Analytica Chimica Acta 857 (2015) 1–27
Contents lists available at ScienceDirect
Analytica Chimica Acta journal homepage: www.elsevier.com/locate/aca
Review
Sample preparation methods for determination of drugs of abuse in hair samples: A review Susanna Vogliardi a , Marianna Tucci a , Giulia Stocchero b , Santo Davide Ferrara a , Donata Favretto a, * a b
Department of Cardiological Toracic and Vascular Sciences, University Hopsital, University of Padova, Via Falloppio 50, I-35121 Padova, Italy Forensic Toxicology and Antidoping, University Hospital, University of Padova, Italy
H I G H L I G H T S
G R A P H I C A L A B S T R A C T
Sample preparation methods for drugs of abuse in hair are reviewed. Collection, extraction, decontamination and purification are reviewed. Sample preparation and extraction methods are compared.
A R T I C L E I N F O
A B S T R A C T
Article history: Received 14 January 2014 Received in revised form 28 June 2014 Accepted 30 June 2014 Available online 7 August 2014
Hair analysis has assumed increasing importance in the determination of substances of abuse, both in clinical and forensic toxicology investigations. Hair analysis offers particular advantages over other biological matrices (blood and urine), including a larger window of detection, ease of collection and sample stability. In the present work, an overview of sample preparation techniques for the determination of substances of abuse in hair is provided, specifically regarding the principal steps in hair sample treatmentdecontamination, extraction and purification. For this purpose, a survey of publications found in the MEDLINE database from 2000 to date was conducted. The most widely consumed substances of abuse and psychotropic drugs were considered. Trends in simplification of hair sample preparation, washing procedures and cleanup methods are discussed. Alternative sample extraction techniques, such as head-space solid phase microextraction (HS-SPDE), supercritical fluid extraction (SFE) and molecularly imprinted polymers (MIP) are also reported. ã 2014 Elsevier B.V. All rights reserved.
Contents 1. 2. 3.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Decontamination of hair samples . . . . . . . . . . . . Extraction of drugs from hair . . . . . . . . . . . . . . . 3.1. Extraction with methanol . . . . . . . . . . . . . 3.2. Extraction with acetonitrile . . . . . . . . . . . 3.3. Extraction by aqueous or buffer solutions 3.4. Extraction with solvent mixtures . . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
* Corresponding author. Tel.: +39 498272225; fax: +39 49663155. E-mail address:
[email protected] (D. Favretto). http://dx.doi.org/10.1016/j.aca.2014.06.053 0003-2670/ ã 2014 Elsevier B.V. All rights reserved.
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. . . . . . .
. 2 . 3 . 4 . 4 . 16 . 16 . 20
2
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
4. 5. 6.
3.5. Digestion with aqueous NaOH . . . . . . . 3.6. Enzymatic digestion . . . . . . . . . . . . . . . 3.7. Extraction with urea and thioglycolate 3.8. Microwave-assisted extraction . . . . . . . Cleanup of hair extracts . . . . . . . . . . . . . . . . . . Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
21 21 21 21 21 22 23 23
Susanna Vogliardi is a postdoctoral fellow in Forensic Toxicology at the University of Padova, Italy. She is working in the Laboratory of Forensic Toxicology and Antidoping, Padova University Hospital. As a researcher, she has developed new extraction and analytical methods to quantify drugs and metabolites in blood and urine, and in hair.
Marianna Tucci is a postdoctoral fellow in Forensic Toxicology at the University of Padova, Italy. She has experience in mass spectrometry coupled with gas chromatography (GC–MS), mass spectrometry combined with liquid chromatography (LC–MS) and high resolution mass spectrometry (HRMS) techniques in hair analysis. She is currently working in the field of untargeted metabolomics research at the Laboratory of Forensic Toxicology and Antidoping of Padova University Hospital.
Giulia Stocchero actually works as a Chemical Director at the Forensic Toxicology and Antidoping, University Hospital of Padova, Italy. She is responsible for screening and confirmation of ethanol and drugs of abuse. In the research field she is involved in clinical and toxicological analysis of cheratinic specimens.
Santo Davide Ferrara is Full Professor of Legal Medicine of the University of Padova, Italy, President of the School of Medicine of Padova, Director of the Specialization School of Legal Medicine, Director of the Forensic Toxicology and Antidoping Structure of the University Hospital, President of the International Academy of Legal Medicine (IALM). He is author of more than 350 ?publications including books and articles in both national and international, peer reviewed journals. He has acted as Chairman, moderator and speaker in numerous International conferences/congresses in the areas of Legal Medicine, Forensic Sciences, Toxicology and other related disciplines.
Donata Favretto is a Professor of Forensic Toxicology at the University of Padova, Italy. She is responsible of the Laboratory of Forensic Toxicology and Antidoping, Padova University Hospital. She is a member of “The International Association of Forensic Toxicologists” (TIAFT). In 2006 ?she was awarded the best Published Paper of the Young Scientists Committee of the TIAFT. She is a member of the board of the Society of Hair Testing. Her research activity is committed to forensic toxicology and legal medicine and to the technological develpments in analytical chemistry and mass spectrometry.
1. Introduction In recent years, analysis of the hair matrix has gained increasing importance in the determination of substances of abuse, with implications in the areas of forensic and clinical toxicology [1–3]. The time window for the detection of most substances of abuse in hair compared to the more classic biological specimens (blood and urine), whose time limit is a few days, is wider and varies from weeks to months, depending on the actual length of the hair [1,2]. Therefore, the use of hair is complementary to that of blood and urine samples, matrices of choice for obtaining short-term information about an individual’s intake of substances; the analysis of hair allows the assessment of use over time, even when the substance has already been eliminated from the organism for some period. By means of segmental analysis, it is possible to verify the chronic intake of a substance and estimate the period of use, considering an average hair growth rate of about
1 cm/month. Compared to the analysis of blood and urine, the analysis of hair has further advantages, such as stability of the incorporated substances for long periods, the non-invasive sample collection procedure and the fact that the sample cannot be easily adulterated [4]. In the forensic field, the analysis of hair is used in cases where it is necessary to exclude or demonstrate a state of addiction, to provide data with medical-legal value. It is therefore utilized in verifying/disproving driving fitness, the entrustment of the custody of minors and criminal responsibility, as well as in the post-mortem context for deaths connected to the use of drugs and pharmaceuticals, in cases of sexual violence facilitated by the administration of substances, in the work environment (workplace drug testing (WDT)), in the issuance of firearms licences and in anti-doping controls. In the clinical setting, analysis of the hair matrix is utilised for the recognition of drugs and substances of abuse, for the control of prenatal exposure to drugs and substances
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
3
[(Fig._1)TD$IG]
of abuse, in the therapeutic monitoring of drugs and as a long-term follow-up for patients in drug replacement therapy or for those being discharged from rehabilitation centers. Hair analysis to prove single drug use is also applied in drugfacilitated crimes. Due to improved analytical sensitivity, hair analysis can be useful for detection of single drug dose exposure [5]. Hair has been suggested as a valuable specimen in situations where, because of a delay in reporting the crime, natural processes have eliminated the drug from typical biological specimens [6]. The use of liquid chromatography coupled with mass spectrometry (LC-MS/MS) or high resolution mass spectrometry (LC–HRMS) allows the detection of a single dose of most sedatives [7–11]. The precise mechanisms responsible for the incorporation of xenobiotics in the hair have not yet been completely clarified [12]. However, it is believed that the substances penetrate the keratin matrix mainly by passive diffusion from blood capillaries and can also be deposited in the hair shaft through the diffusion of sweat, from sebaceous secretions or during the formation of hair from cellular compartments, which are present at some depth. This multi-compartmental model has been demonstrated by Henderson [4,13]. The incorporation of xenobiotics in the hair from the bloodstream is highly dependent on the nature of the substance incorporated (structure, chemical properties) and the physical/ physiological characteristics of the individual. From a structural point of view, this incorporation is influenced by melanin content in the matrix and is regulated by the pharmacological principles of the distribution of the substance. Neutral lipophilic organic molecules can easily penetrate and spread, while for hydrophilic molecules or medium-sized organic ions, the cell membranes may constitute an impenetrable barrier. Substances may also be deposited from the external environment [4]. Acid or basic substances that are highly ionized at physiological pH can reach the cells after protonation or deprotonation, respectively, to a neutral form. It follows that both the pKa of the substance and the pH of the cells are important factors. Considering that the intracellular pH of keratinocytes and melanocytes is more acidic than that of plasma [14] and that melanin’s affinity for certain basic molecules has been demonstrated in vitro [15,16], it can be understood that lipophilic and basic substances accumulate more easily in the cells of the matrix, particularly if there is a high degree of pigmentation, while acidic substances are detected in the hair in very low concentrations. In most cases, drug metabolism leads to increased hydrophilicity; therefore, polar metabolites, such as benzoylecgonine, morphine and amphetamine are incorporated to a lesser extent than their precursors, namely more lipophilic substances, cocaine, 6-monoacetylmorphine and methamphetamine. The retention and stability of xenobiotics in hair is generally good, demonstrated by segmental analysis of the samples of subjects subjected to constant doses of a particular substance. However, there is no inter-individual correlation between the frequency of intake of a substance and its concentration in the hair; the efficiency of incorporation differs greatly from individual to individual and is influenced by the pigmentation of the keratinic matrix, especially for basic substances. Furthermore, cosmetic treatments with aggressive chemical agents can damage the hair structure and result in a decrease of 1–90% of the initial concentration of the substance [17]. Hair analysis consists of several stages: collection and sample storage, decontamination, extraction of the target analytes from the matrix, purification of the extracts, instrumental analysis, and evaluation and interpretation of the results, as illustrated in Fig. 1. Generally, the sample (20–200 mg) is collected from the nuchal area of the posterior vertex of the head, cutting as close as possible to the root; the length is measured and the proximal and distal
Fig. 1. Steps of hair analysis.
portions identified. The decontamination phase consists of one or more washings of the sample in order to eliminate possible external contamination. The extraction of the analytes from the hair can be achieved by various methods, which differ according to the nature of the analytes themselves and the analytical method to be employed. The objective is to obtain a good extraction yield without chemically degrading the analytes and their metabolites. Before instrumental analysis, purification (clean-up) of the extract is often required. Instrumental analysis may consist of a generic screening followed by a confirmation analysis using chromatographic methods—either gas chromatography (GC) or liquid chromatography (LC), coupled to mass spectrometry (MS) detectors. Recent advantages in the sensitivity of the analytical techniques (GC-MS/MS, GC-(time-of-flight) TOF/MS, LC-MS/MS, high resolution MS (LC–HRMS)) [18,19] have provided low limit of detection (LOD) and limit of quantification (LOQ) values in the ppm range for most drugs of abuse. Finally, interpretation of the analytical results is an important stage of the process with regard to both the quantification of the analytes and the estimation of the temporal window of intake. In the present overview, hair analysis sample preparation methods are reviewed and discussed for the most widely consumed substances of abuse or psychotropic drugs: cocaine and its metabolites, opiates, amphetamines, cannabinoids, methadone and its metabolites, and benzodiazepines. Decontamination, extraction and purification of the sample are examined, as these stages are the most costly in terms of analysis time and they contain the greatest number of variables. 2. Decontamination of hair samples The decontamination of a hair sample consists of one or more washing steps, the purpose of which is to remove various environmental contaminants that could create interference at the analytical level, and to exclude any external contamination
4
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
with the analytes of interest [5,12]. At the analytical level, cosmetic product residues, sweat, sebum and dust deposited on the hair can cause an increase in background noise. For an accurate interpretation of the analytical results, it is necessary to distinguish between the presence of analytes due to external contamination and those detected due to the ingestion of a given active substance. It is possible that substances have been passively deposited from the external environment, causing false positive results. In order to distinguish passive contamination from active consumption, a thorough examination of the wash solutions obtained during hair decontamination is required. A specific washing sequence and the ratio of drug concentrations in the wash versus hair may be used to differentiate passive contamination and systemic incorporation [20]. As an example, Schaffer et al. [21] demonstrated the effectiveness of consecutive washes with isopropanol and phosphate buffer, instead of a single wash with methanol, for removing cocaine contamination. The analytical outcome of hair analysis can be strongly affected by the wash procedure used [20]. As much as possible, the solvents used for washing must eliminate the exogenous substances deposited on the outer part of the hair without extracting those incorporated within it. Certain criteria can be used to evaluate external contamination along with the determination of metabolites in a specific ratio with respect to the parent substance as evidence that an intake has occurred [21]. Protic solvents, such as phosphate buffer or methanol, promote extraction in the washing step by swelling the hair, thereby possibly extracting analytes from the inner part of the hair. In contrast, the use of non-protic solvents, such as dichloromethane or acetone, is more advantageous because they do not swell the hair and should ideally remove only the surface analytes. The various procedures proposed for the decontamination of hair samples are summarized in Tables 1–5. Generally, the decontamination of the sample is carried out by subjecting it to a sequence of washes using different solvents. The washing procedures most frequently used are those which utilise one or two washes with non-protic solvents, such as dichloromethane [8–10,22–35,36–44] or a single short wash with the protic solvent methanol [45–55]. In contrast to these two procedures, which are used for all the considered classes of drugs (cocaine, opiates, methadone, cannabinoids, amphetamines and benzodiazepines), washing with isopropanol alone is used for cannabinoids only [56–58]. Among the protic solvents, besides methanol, water [59,60] and ethanol [61] are also used in selected cases. Sequences of two washes with non-protic solvents can also be employed; for example, for the analysis of benzodiazepines, a wash step with isooctane and acetone is used [62], whereas hexane and acetone are used for the analysis of amphetamines, cocaine and opiates [63]. Despite the risk of hair swelling, combinations of protic solvents are often employed. The surfactant sodium dodecyl sulphate (SDS) followed by water and methanol is used for the analysis of amphetamines, cocaine, opiates, benzodiazepines [64–67], whereas SDS followed by water [68], methanol [69] or ethanol [70] is used for the analysis of amphetamines. Sequences of washing with water/methanol or water/ethanol are also used for the analysis of benzodiazepines [71–73] as well as buffer solutions followed by propanol [74,75]. Wash combinations with protic and non-protic solvents are often encountered: amphetamines, methadone, cocaine, opiates, benzodiazepines are indifferently extracted after washes with SDS and water followed by either acetone [19,76,77] or dichloromethane [78–80] or by isopropanol followed by dichloromethane [81]. Amphetamines are also extracted using water followed by ether and dichloromethane [82] or ethanol and dichloromethane
[83]. Decontamination of hair samples for the analysis of cannabinoids can be performed by sequences of washing with water followed by either ether and acetone [84] or ether and dichloromethane [85–88]. Other combinations of washing reverse the solvents using a sequence of non-protic solvent followed by an aprotic one; they are indifferently used for decontamination before the extraction of cocaine, methadone, opiates, benzodiazepine, amphetamines, cannabinoids; in the last case, acetone and water [89–96], and dichloromethane followed by both water and methanol [97–102] or by isopropanol [103] are used. For the analysis of amphetamines, decontamination steps with dichloromethane, water and acetone [104] and dichloromethane, acetone and methanol [105] are also used. Dichloromethane followed by methanol is used instead for the analysis of benzodiazepines [106]. Shampoo (i.e., a solution containing surfactants) is sometimes used when decontaminating hair for the assessment of amphetamines, benzodiazepines and cannabinoids [107]. From this analysis, it is apparent that an optimal, universally recognized procedure for the decontamination of hair has not been identified; for example, for the same class of cocaine, very different wash methods have been used, with either protic or non-protic solvents or combinations of the two. However, regardless of the nature of the analytes being investigated, it is noted that acetone, dichloromethane and water are the most frequently used solvents. These substances do not have the drawback of partially extracting the analytes themselves; water washing is generally rapid and typically used by the subject during routine hair care. 3. Extraction of drugs from hair At present, only a few direct methods for the detection of organic substances in hair have been described; these methods require the separation of analytes from the solid keratinic matrix. The extraction of analytes from the intact hair matrix may be realised (i.e., by direct suspension of hair in solvents; see Sections 3.1–3.5) or by digestion of the hair matrix itself, followed by extraction (see Sections 3.6 and 3.7). The purpose of these procedures is to selectively and quantitatively extract the analytes of interest from the hair without chemically modifying them. There is currently no universal procedure capable of ensuring optimum yields for all classes of substances; in order to choose the most appropriate extraction method, the chemical structure of the analyte to be extracted and its sensitivity to agents used in the preparation of the sample must be considered. After decontamination and before extraction, the sample is generally cut into fragments of 1–3 mm in length, or preferably, pulverized by a ball mill in order to facilitate the subsequent extraction procedure, rendering a large as possible surface for penetration of the solvent. Extraction of the analytes from solid hair can be done directly with solvents (a sort of solid/liquid extraction), as described in Sections 3.1–3.4, facilitated by grinding of the hair matrix, or by using an ultrasonic bath. The last approach is used more frequently with methanol extraction (see Section 3.1): in this case, hydrophilic methanol penetrates the hair matrix leading to swelling and drug liberation via diffusion. Methanol can dissolve neutral, hydrophilic and lipophilic compounds, while ultrasonication effectively degrades the structure of the hair. Two interesting alternative approaches are microwave-assisted extraction (MAE) [108] and micro-pulverized extraction, in which pulverization and extraction occur simultaneously [19,109] (also see Section 3.4).
Table 1 Extraction with methanol. Class
Amphetamines
Compound
Sample amount (mg)
Washing
Sample cleanup type
Sample clean-up details
Derivatization
A, MA, MDA, MDMA
10
Dichloromethane
1 mL methanol 18 h 56 C
HS SPE
Oasis HCX 60
20
Shampoo, deionized water, acetone, air dried overnight
PTFE
1 mL methanol/water (1:1 v 1:v 1) 0.45 mm PTFE syringe filter
MDMA
50
A, MA,MDA, MDMA A, MA,MDA, MDMA,MDEA A, MA,MDA, MDMA A, MA,MDA, MDMA, MDEA
10
Dichloromethane, acetone, methanol Water, acetone
20
n-Hexane, acetone
4 mL methanol, 8 h at 50 C + overnight at room temperature methanol pH 7.4, 50 C, 5 h 1 mL methanol 50 C, 1 h 1 mL methanol
BSTFA:MSTFA (4:1 v 1:v 1) + 1% TMCS No
MA
2 mL methanol 45 C, 18 h 1 mL methanol 40 C, 16 h
No
No
LLE
Hexane/ethylacetate (90:10 v 1:v 1)
methanol/TFA 25 C overnight 4 mL methanol, 8 h at 50 C + overnight at room temperature methanol 38 C, 16 h
SPE
Dichloromethane
LLE microextraction PTFE
Analytical techniques
IS
GC–MS
A-d5
LC–TOFMS
LOD (ng mg
LOQ (ng mg
1
)
References 1
)
0.2
0.4
[38]
0.05
0.15
[107]
HPLC–DAD 0.2 mm PTFE syringe filter
HFBA
[105]
GCKMS
A-d8
0.027
0.1
[95]
LC-MS/MS
A-d3
0.2
0.2
[63]
Half MTBSTFA/ MBTFA 90 C, 1 h HFBA/ethyl acetate
GC–MS
MDA d5
0.02
GC–MS
Bond Elut Certify
BSTFA
GC–MS
MDMA-d5, A-d5, MA-d5, MDA-d5, MDEA-d5 A-d5, MA-d5, MDA-d5, MDEA-d5, MDMA-d5
Centrifugated, evaporated N2
1 mL methanol/water (1:1 v 1:v 1) filtered 0.45 PTFE syringe filter
No
LC–TOFMS
Evaporated N2 and filtrated
PVDF microporous membrane CLEAN SCREEN COLUMN/rapid trace
Dichloromethane
25
Dichloromethane
Benzodiazepines
A, MA,MDA, MDMA, MDEA Diazapem
20
Shampoo, deionized water, acetone, air dried overnight
10
Methanol, water, methanol
30
Water, methanol
methanol 38 C, 16 h
SPE
100
Dichloromethane
2 mL methanol 55 C, 15 h
Evaporated N2
20
Dichloromethane, water, methanol
1 mL methanol 45 C, 2 h
LLE
Dichloromethane
2 mL methanol 45 C, 18 h
Evaporated N2
no
Half MTBSTFA/ MBTFA 90 C, 1 h
GC–MS
Cannabinoids
27Benzodiazepines and metabolites Diazepam, oxazepam, nordiazepam, lorazepam, temazepam midazolam 10Benzodiazepines and metabolites 26Benzodiazepines and metabolites Diazapem, desmethyl-diaz, oxazepam, temazepam THC, CBD, CBN
20
Shampoo, deionized water, acetone, air dried overnight
Centrifugated, evaporated N2
1 mL methanol/water (1:1 v 1:v 1) filtered 0.45 PTFE syringe filter
No
LC–TOFMS
THC, CBD, CBN
50–100
MTBSTFA
GC–MS
THC-COOH-d3
THC, CBD, CBN
50
Water, petrol ether, methanol Dichloromethane
4 mL methanol, 8 h at 50 C + overnight at room temperature 4 mL methanol 5h 1 mL methanol 40 C, 16 h
HFBA/ethyl acetate
GC–MS
THC-d3
1-chlorobutane
SPE LLE
MSTFA
hexane/ethylacetate (90:10 v 1:v 1)
[41]
0.03
0.05
[26]
0.0125
0.04
[107]
LC-MS/MS
Diazepam-d5
0.25
0.25
[71]
GC–MS
Lorazepam-d4
5
10
[72]
LC-MS/MS
Nitrazepam-d5
0.5 pg mg
LC-MS/MS
7-Aminoclonazepam-d4
MDA-d5
1
1.7 pg mg
0.5– 10 pg mg
1
[102] 1
0.11
0.0125
[37]
[30]
0.04
0.1 pg mg
[107]
1
[115] [41]
5
50
[30]
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
Extraction procedure
6
Table 1 (Continued) Class
Compound
Sample amount (mg)
THC, CBD, CBN
Cocaine
Opiates
Acetone, petrolether Dichloromethane
5 h at 50 C – ultrasonication 12 mL methanol 18 h, 56 C
Shampoo, deionized water, acetone, air dried overnight
4 mL methanol, 8 h at 50 C + overnight at room temperature 1 mL methanol 52 C, overnight
COC, BZE, CE, norCOC
10
COC, BZE
20
COC, BZE
10
COC, BZE, CE COC, BZE, CE
20 50
COC, norCOC, BZE, EME, CE
20
COC, BZE, CE
50
Dichloromethane
COC,BZE
20
Dichloromethane
COC
50
Dichloromethane
COC, EME, BZE, CE
50
Dichloromethane
COC, EME, BZE, CE MTD
20
MTD, EDDP
20
n-Hexane, acetone Water, petroleum benzine, dichloromethane
Dichloromethane Shampoo, deionized water, acetone, air dried overnight
MTD, EDDP
Dichloromethane
MTD
Dichloromethane
MTD
10
Dichloromethane
MTD
50
Dichloromethane
MOR, COD, 6MAM, HMOR, OXYMOR, HCOD HER, MOR
10
Dichloromethane
20
Extraction procedure
1 mL methanol 4 mL methanol 5 h, 50 C 1250 mL methanol 37 C, 3h 2 mL methanol 50 C, 18 h 990 mL methanol 40 C, 4 h 2 mL methanol 40 C, 18 h 4 mL methylene chloryde/ isopropanol/ heptane (50:17:33 v 1: v 1:v 1) 2 mL methanol 45 C, 18 h 4 mL methanol, 8 h at 50 C + overnight at room temperature 2 mL methanol 60 C overnight 2 mL methanol 45 C, 18 h 2 mL methanol 45 C, 18 h 16 mL methanol 56 C, 18 h 2 mL methanol 40 C, 18 h 5 mL methanol 56 C, 18 h
Sample cleanup type
Sample clean-up details
Derivatization
Analytical techniques
IS
HPLC–ED HS SPE
oasis HCX 71
Centrifugated, evaporated N2
1 mL methanol/water (1:1 v 1:v 1) filtered 0.45 PTFE syringe filter
SPE
SPE
Clean screen SPE columns
SPME
polydimethylsiloxane fiber, 20 min
SPE
Bond Elut Certify
LLE
No
No
Centrifugated, evaporated N2
1 mL methanol/water (1:1 v 1:v 1) filtered 0.45 PTFE syringe filter
No
No
HS SPE
Oasis HCX 75
SPE
Bond Elut Certify
HS SPE
oasis HCX 64
BSTFA:MSTFA (4:1 v 1:v 1) + 1% TMCS No
MSTFA
Acetonitrile, pyridine, butylchloroformate
GC–MS
LOD (ng mg
1
)
LOQ (ng mg
300 COC-d3
References 1
) [116]
0.13
0.4
[38]
LC–TOFMS
0.005
0.015
[107]
Enzyme-linked immunosorbent assay + GC–MS LC-MS/MS GC–MS
0.1
COC-d3 COC-d3
0.05 0.01
0.05 0.11
[63] [42]
LC-APCI-MS/MS
COC-d3
0.0085
0.017
[111]
GC–MS
COC-d3
0.1
0.1
[112]
LC-MS/MS
COC-d3; BZE-d3
0.001
0.01
[113]
Pyridine/propionic acid anhydride BSTFA/TMCS
GC–MS GC–MS
COC-d3, CE-d3, BZE-d3
Half MTBSTFA/ MBTFA 90 C, 1 h no
GC–MS
PCP-d5
[110]
0.2
[28] [41]
0.12
[30]
LC–TOFMS
0.05
0.15
[107]
GC–MS
0.1
0.1
[114]
Half MTBSTFA/ MBTFA 90 C, 1 h MTBSTFA
GC–MS
PCP-d5
0.15
[30]
GC–MS
PCP-d5
0.4
[31]
BSTFA:MSTFA (4:1 v 1:v 1) + 1% TMCS Pyridine/propionic acid anhydride BSTFA:MSTFA (4:1 v 1:v 1) + 1% TMCS No
GC–MS
MTD-d3
0.2
GC–MS GC–MS
LC–TOFMS
0.6
0.3 COD-d3
[38]
[28]
0.2
0.6
[38]
0.0125
0.04
[107]
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
Methadone
Washing
Shampoo, deionized water, acetone, air dried overnight MOR, COD, 6MAM MOR, COD, 6MAM MOR, COD, norCOD, 6-MAM, HER, acetylCDO MOR, COD, norCOD, 6-MAM
4 mL methanol, 8 h at 50 C + overnight at room temperature
Centrifugated, evaporated N2
1 mL methanol/water (1:1) filtred 0.45 PTFE syringe filter
No
No
n-Hexane, acetone
1 mL methanol
50
Water, petroleum benzine, dichloromethane
4 mL methanol 50 C, 5 h
SPE
1.25 mL methanol 37 C, 3h 990 mL methanol 40 C, 4 h 2 mL methanol 40 C, 18 h 4 mL methylene chloryde/ isopropanol/ heptane (50:17:33 v 1: v 1:v 1) methanol/TFA 25 C overnight 2 mL methanol 45 C, 18 h
SPE
20
MOR, COD, 6MAM MOR, COD, 6MAM, HER MOR, COD, 6MAM
20
Dichloromethane
50
Dichloromethane
50
Dichloromethane
MOR, COD, 6MAM MOR, 6-MAM
25
Dichloromethane Dichloromethane
MSTFA
Clean screen SPE columns
SPE
Bond Elut Certify
LC-MS/MS
0.01
LC-MS/MS
0.2
0.2
[63]
GC–MS
HER-d9
0.02
0.04
[42]
LC-APCI-MS/MS
COD-d3
0.0415
0.083
[111]
LC-MS/MS
MOR-d3, COD-d3, 6-MAM-d6
0.01
0.05
[113]
GC–MS
LLE
Pyridine/propionic acid anhydride BSTFA/TMCS
GC–MS
MOR-d3, COD-d3, 6-MAM-d3
SPE
HFBA
GC–MS
MTBSTFA/MBTFA 90 C 1 h
GC–MS
MOR-d3, COD-d3, 6-MAM-d3 PCP-d5
No
No
[109]
0.05
[28] [41]
0.05–0.08
0.08–0.1
[26]
0.4
[30]
Basic methanol Class
Amphetamines
Benzodiazepines
Cannabinoids
Compound
Sample amount (mg)
Washing
A, MA,MDA, MDMA 20
Water
A, MA,MDA, MDMA, MDEA Alprazolam, alfa10 hydroxyalprazolam
Water, acetone
8-Benzodiazepines and metabolites
–
0.1 % aqueous SDS, water, dichloromethane
7-Benzodiazepines and metabolites
30
0.1% SDS, water, dichloromethane
24Benzodiazepines and metabolites
30
Water, acetone, hexane
5-Benzodiazepines
50
Dichloromethane, water, methanol
THC-COOH
15
Extraction procedure
Sample cleanup type
Sample clean-up details
1 mL, 1 M NaOH 70 C, 30 min 1 M NaOH 100 C, 30 min
LLE
Cyclohexane
SPE
1 mL phosphate buffer pH 8.7 overnight 37 C
LLE
Cleanscreen ZSDAU020 2 mL ethyl acetate
1.5 mL methanol/25% aqueous ammonium hydroxide solution (20:1, v 1:v 1) 1.5 mL methanol/ 25% ammonium hydroxide (20:1, v 1:v 1)
SPE
SPE
Derivatization
CSEI
Benzylamine
HFBOPCl
GC–MS
A-d5
50 mL acetonitrile and 50 mL BSTFA (1% TMCS)
GC–MS
Alprazolam-d5
7
20
[118]
LC-MS/MS
7Aminoflunitrazepamd7
0.03
0.05
[78]
LC-MS/MS
7Aminoflunitrazepamd7
1 pg mg
1.5 mL methanol shaker 90 min/5 mM ammonium formate buffer pH 3.5 HCOOH/methanol 1:1 1 mL methanol/ammonia (97.5:2.5 v 1:v 1) 45 C, 2 h
Centrifugated, evaporated N2
LC-MS/MS
Alprazolam-d5
Centrifugated, evaporated N2
Methylclonazepam
0.5 mL methanol 0.5 mL, 10 N KOH 70 C, 30 min
SPE
HPLC reverse phase GC-MS/MS
Narc-1 SP cartridge
References
IS
World wide monitoring clean screen columns ZSDAU 020 World wide monitoring clean screen columns ZSDAU 020
Pentafluoropropanol/ pantafluoropropionic anhydride
THC-COOH-d3
LOD (ng mg
LOQ (ng mg
Analytical techniques
1
)
0.04 g mL
1
1
)
0.14 g mL
1
[59] [92]
1
1.6 pg mg
1
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
20
No
[79]
[117]
0.2
0.3–0.45
[100]
0.0001
[115]
7
Acidic methanol 8
Class
Amphetamines
Compound
Washing
A, MA,MDA, MDEA, MDMA
7-16
Water, methanol
A, MA
10
Methanol/HCl 1% 38 C, 20 h
Evaporated N2
A, MA
10
Evaporated N2
A, MA
10
A, MA
10
A, MA,MDA, MDEA, MDMA
25
Dichloromethane
A, MA,MDA, MDMA,MDE, MBDB, DOM, BDB
50
A, MA
30
10% SDS, 1 mL water twice, 10 mL acetone Acetone, water, twice
1 mL methanol/ HCl 1% 20 h 1% HCl methanol 20 h, 38 C 1% HCl methanol 20 h, 38 C 2 mL methanol/ TFA (8.5:1.5 v 1:v 1) 25 C, 16 h Methanol 2% HCl
A, MA
10
SDS 1%, water, methanol
A, MA,MDA, MDEA, MDMA
0.1% SDS, water
A, MA
0.1% SDS, ethanol
A, MA, MDA, MDMA
Benzodiazepines alprazolam, clobazam, N-desmethyl clobazam, clonazepam, 7-amino clonazepam, diazepam, nordiazepam, lorazepam, midazolam, oxazepam, temazepam, triazolam, zopiclone, N-desmethyl zopiclone Opiates MOR, COD, 6-MAM
50
Water, ethanol
25
Dichloromethane
Extraction procedure
Sample cleanup type
Sample clean-up details
1 mL methanol/ 1% HCl 20 h
2 mL methanol/ 5 M HCl (20:1, v 1:v 1) ultrasonication 1h 1 mL methanol/ 5 M HCl (20:1 v 1:v 1) soaked 50 C overnight Methanol/5 M HCl sonicated 1 h and incub 24 h room temperature Methanol/5% TFA incubation overnight room temperature Methanol/5% TFA incubation overnight room temperature 3 mL TFA/ methanol (1:50, v 1:v 1) 16–18 h room temperature 2 mL methanol/ TFA (8.5:1.5 v 1:v 1) 25 C, 16 h
Bond Elut Certify
References
IS
GC–MS
A-d5
[119]
GC–MS
A-d5
[120]
GC–MS
A-d5
GC–MS
A-d5,MA-d5
[122]
100 mL TFAA/ ethylacetate
GC–MS
MA-d5
[43]
HFBA 70 C, 3 min
GC–MS
A-d5
0.02
GC/MS/MS
MPDA
0.1–0.2
Centrifugated, evaporated N2
LOD (ng mg
LOQ (ng mg
Analytical techniques
TFA anhydride 65 C, 15 min TFA/ethyl acetate (1:1 v 1:v 1) TFA/ethyl acetate 100 mL TFAA/ ethylacetate
Evaporated N2
SPE
Derivatization
1
)
0.125
1
)
[121]
0.05
[25]
[76]
Evaporated N2
TFAA 70 C, 30 min
GC–HRMS
A-d5
0.021
SPE online
TFA
LC–MS
Dibenzylamine
0.02
[65]
Filtered and evaporated N2
DIB-Cl Fluorescence derivatization
HPLC–FL
MPPA
0.08
[68]
Filtered and evaporated N2
DIB-Cl Fluorescence derivatization
HPLC–FL
54 pg mg
Filtered and evaporated N2
DIB-Cl Fluorescence derivatization
HPLC–FL
0.011–0.2
[123]
[73]
LLE
dichloromethane
SPE
Bond Elut Certify
HFBA 70 C, 30 min
LC-MS/MS
Prazepam
0.00001– 0.006
GC–MS
MOR-d3
0.02
0.069
1
[124]
[70]
0.05
[25]
Abbreviations: A, amphetamine; MA, methamphetamine; MDA, 3,4-methylenedioxyamphetamine; MDMA, 3,4-methylenedioxy-N-methylamphetamine; MDEA, 3,4-methylenedioxy-N-ethylamphetamine; THC, D(9)tetrahydrocannabinol; CBD, cannabidiol; CBN, cannabinol; THC-COOH,11-nor-9-carboxy-D9-tetrahydrocannabinol; COC, cocaine; BZE, benzoylecgonine; EME, ecgonine methyl ester; CE, cocaethylene; MDE, methylendioxyethamphetamine; MBDB, N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine; DOM, 2,5-dimethyloxy-4-methylamphetamine; BDB, 3,4-(methylenedioxyphenyl)-2-butanamine; MOR, morphine; COD, codeine; 6-MAM, 6monoacteylmorphine; HER, heroin; HMOR, hydromorphone; HCOD, hydrocodeine; OXYMOR, oxymorphone; MTD, methadone; EDDP, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine.
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
Sample amount (mg)
Table 2 Extraction with acetonitrile. Class
Compound
Sample amount (mg)
Washing
Extraction procedure Sample cleanup type
Sample clean-up details
Analytical techniques
IS
LOD (ng mg-1)
Amphetamines
A, MA, MDA, MDMA
50
Dichloromethane
2 mL acetonitrile 50 C, 12 h
LLE/SPE
LC-MS/MS
A-d5
0.002
[27]
50 Benzodiazepines 7-Aminoflunitrazepam, bromazepam, oxazepam, lorazepam, alprazolam, clonazepam, nordiazepam, triazolam, flunitrazepam, tetrazepam, lormetazepam, diazepam Cannabinoids THC 50
Dichloromethane
2 mL acetonitrile 50 C, 12 h
LLE/SPE
LLE:4 mL hexane: ethylacetate (55:45 v 1: v 1) SPE:Strata-X cartridge LLE:4 mL hexane: ethylacetate (55:45 v 1: v 1) SPE:Strata-X cartridge
LC-MS/MS
COC-d3
0.002
[27]
Dichloromethane
2 mL acetonitrile 50 C, 12 h
LLE/SPE
LC-MS/MS
THC-d3
0.05
[27]
Cocaine
LLE:4 mL hexane: ethylacetate (55:45 v 1: v 1) SPE:Strata-X cartridge LLE:4 mL hexane: ethylacetate (55:45 v 1: v 1) SPE:Strata-X cartridge
LC-MS/MS
COC-d3
0.002
[27]
50
Dichloromethane
2 mL acetonitrile 50 C, 12 h
LLE/SPE
COC, BZE
50
2 mL acetonitrile sonicated 2 h
MIP
Methadone
MTD
50
Water, water/methanol (50:50:50 v 1:v 1 1)/ dichloromethane Dichloromethane
2 mL acetonitrile 50 C, 12 h
LLE/SPE
Opiates
MOR, 6-MAM, COD
50
Dichloromethane
2 mL acetonitrile 50 C, 12 h
LLE/SPE
LC–MS
LLE:4 mL hexane: ethylacetate (55:45 v 1: v 1) SPE:Strata-X cartridge LLE:4 mL hexane: ethylacetate (55:45 v 1: v 1) SPE:Strata-X cartridge
0.01
0.07
References
[125]
LC-MS/MS
MTD-d3
0.002
[27]
LC-MS/MS
MOR-d6
0.005
[27]
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
COC, BZE
LOQ (ng mg-1)
Abbreviations: A, amphetamine; MA, methamphetamine; MDA, 3,4-methylenedioxyamphetamine; MDMA, 3,4-methylenedioxy-N-methylamphetamine; THC, D(9)-tetrahydrocannabinol; COC, cocaine; BZE, benzoylecgonine; MOR, morphine; COD, codeine; 6-MAM, 6-monoacteylmorphine; MTD, methadone; MIP, molecularly imprinted polymer.
9
10
Table 3 Extraction by aqueous or buffer solutions. Class
Amphetamines
Sample amount (mg)
Washing
20
Water, acetone, ultrasonic bath Dichloromethane, distilled water, acetone Dichloromethane, isopropanol, acetone 1% SDS, water, methanol
A, MA,MDA, MDMA,MDE, MBDB A,MA, EPHEDRINE
50
A, MA, MDA, MDMA
50
MA
10
A, MA,MDA, MDMA, MDEA
10
0.1% SDS, water, dichloromethane
A, MA,MDA, MDMA
20
Twice 5 mL 0.1% Tween 80 10 min, distilled water
A, MA
10
A, MA,MDA, MDMA
20
Methanol
MDMA
50–200
Water
A, MA,MDA, MDMA, MDEA, MBDB
10
Water, acetone
COD, MOR, 6-MAM
50
Methanol
MOR
70
MOR, COD, 6-MAM
50
Methanol
MOR, COD, 6-MAM
20
Methanol
MOR, 6-MAM, COD
50
MOR, COD
10
Dichloromethane, isopropanol, acetone 1% SDS, water, methanol
MOR, COD, 6-MAM, DHC
10
0.1% SDS, water, dichloromethane
Extraction procedure
Sample clean-up type
Sample clean-up details
Derivatization Analytical techniques
IS
1 M, HCl 60 C, 60 min 1 mL, 0.1 M HCl 55 C, 16 h
HS–SPME
103 micro PDMS 5min 90 C 4 mL ethylacetate twice
No
GC–MS
MDPA
0.37–1.61
1.11–4.83
GC–MS
MA-d5
4; 0.2; 0.1
10; 0.4; 0.4 [104]
2 mL, 0.1 M HCl 50 C overnight
SPE
GC–MS
MDA-d5,coc-d3, BE-d3,6-MAM-d6
1 mL, 0.1 M HCl 2 h room temperature 1.5 mL phosphate buffer pH 5 45 C, 18 h 500 mL, 0.01% formic acid 4 h
LLE
Ethylacetate
CSEI-SweepMEKC
SPE
Bond Elut Certify
LC-MS/MS
1,1Dimethylbiguanide HCl A-d5
0.08
0.26
[80]
LC-MS/MS
A-d5
0.1
0.5
[127]
2 h incubation enzyme linked immunosorbent assays 1 mL, 0.1 M HCl 37 C, 16 h 1 mL, 0.12 M HCl 45 C overnight 200 mL, 1 M HCl + 200 mg K2CO3 1 mL, 0.1 M HCl 45 C overnight 8 mL, 0.1 M HCl 45 C, 24 h
LLE
Immunoassay test
SPE
BondElut certify
HS–SPME
A-d5
MSTFA
GC–MS
MDPA
50 pg mg
SFE
CO2 modified with methanol (10%) Bond Elut Certify
BSTFA o PFPA
GC–MS
MOR-d3
MSTFA
GC–MS
MOR-d3
0.01–0.03
Bond Elut Certify
MSTFA/TCMS
GC–MS
MOR-d3
0.05
MBTFA and MSTFA + 1% TCMS
GC–MS
MDA-d5,coc-d3, BE-d3,6-MAM-d6 1,1Dimethylbiguanide HCl MOR-d3
Bond Elut Certify
LC-MS/MS
[103]
[67]
[129] 1
0.12
Nalorphine
SPE
1
[91]
[60]
GC–MS
CSEI–Sweep– MEKC
)
[49]
MSTFA
Ethylacetate
References 1
0.1
Bond Elut Certify
LLE
LOQ (ng mg
)
cutoff 200 pg mg
GC GC/ TOFMS LC-MS/MS
MTBSTFA/TFA
1
SPE
1 mL, 0.1 M HCl SPE 45 C overnight 3 mL phosphate SPE buffer 0.1 N pH 5, 45 C, 18 h 2 mL, 0.1 M HCl SPE 50 C overnight 1 mL, 0.1 M HCl 2 h room temperature 1.5 mL phosphate buffer pH 5 45 C, 18 h
MBTFA and MSTFA + 1% TCMS
LOD (ng mg
0.37
[94]
0.02
[45] [133]
0.02–0.09
[46]
0.2
200 pg mg
0.1
[52]
1
[103]
[67]
0.32
[80]
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
Opiates
Compound
MOR, 6-MAM
MOR, COD, 6-MAM Benzodiazepines Diazepam, nordiazepam
20
Methanol
50
Dichloromethane, isopropanol, acetone Dichloromethane
20
50
20
20
20
2 h incubation enzyme linked immunosorbent assays 1 mL, 0.1 M HCl 37 C overnight 2 mL, 0.1 M HCl 50 C overnight 1 mL phosphate buffer pH 8.4
Immunoassay test
SPE
BondElut certify
SPE
MTBSTFA/TFA MBTFA and MSTFA + 1% TCMS
GC GC/ TOFMS GC–MS
cutoff 200 pg mg
COD-d3
[49]
MDA-d5,coc-d3, BE-d3,6-MAM-d6
0.2
[103]
0.0005– 0.005
[33]
LLE
Diethyl ether/ dichloromethane 10:90 v 1:v 1
LC-MS/MS
Diazepam-d5
Isooctane, acetone 1.5 mL phosphate buffer pH 8.4 overnight
LLE
Diethyl ether/ dichloromethane 10:90 v 1:v 1
LC–HRMS
0.5– 7Aminoflunitrazepam- 5 pg mg d7, nitrazepam-d5, nordiazepam-d5
Methylene chloride
1 mL phosphate buffer pH 8.4
LLE
Dichloromethane
LC-MS/MS
Dichloromethane, methanol
1 mL phosphate buffer pH 8.4
LLE
Dichloromethane
1 mL phosphate buffer pH 8.4
LLE
Diethyl ether/ dichloromethane 10:90 v 1:v 1
LC-MS/MS
LC-MS/MS
[129] 1
Diazepam-d5
Halazepam
Diazepam-d5
1– 10 pg mg
1
0.2– 5 pg mg
1
0.1– 1 pg mg
1
[62] 1
[36]
0.5 pg mg
0.3–5 pg mg
1
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
Alprazolam, 7aminiclonazepam, 7amino flunitrazepam, bromazepam, clobazam, diazepam, lorazepam, lormetazepam, midazolam, nordiazepam, oxazepam, temazepam, tetrazepam, triazolam, zaleplon, zolpidem 7-Aminonitrazepam, 7aminiclonazepam, 7amino flunitrazepam, bromazepam, clobazam, diazepam, lorazepam, lormetazepam, midazolam, nordiazepam, oxazepam, alprazolam, triazolam, prazepam, pinazepam, delorazepam, clotiazepam, nitrazepam 7-Aminonitrazepam, 7aminiclonazepam, 7amino flunitrazepam, diazepam, oxazepam, nordiazepam, temazepam, clonazepam, nitrazepam, flunitrazepam, triazolam, alprazolam, midazolam, estazolam, flurazepam Lorazepam, clotiazepam, brotizolam, bromazepam, clomazepam, nitrazepam, temazepam, oxazepam, clobazam, estazolam, demoxepam, pinazepam, lormetazepam, etizolam, midazolam, diazepam, prazepam, triazolam, flurazepam, alprazolam, diazepam, nordiazepam, clonazepam, zolpidem Lorazepam
10
[106] 1
[8]
11
12
Table 3 (Continued) Class
Methadone
Cocaine
Sample amount (mg)
Washing
Extraction procedure
Sample clean-up type
Bromazepam
20
Dichloromethane
1 mL phosphate buffer pH 8.4
LLE
Alprazolam
20
Dichloromethane
1 mL phosphate buffer pH 8.4
LLE
Diazepam, nordiazepam, oxazepam, temazepam
10
0.1% SDS, water, dichloromethane
SPE
Alprazolam, estazolam, lorazepam, clonazepam, diazepam, tetrazepam THC
70
0.1% SDS, water, methanol
1.5 mL phosphate buffer pH 5 45 C, 18 h Borate buffer, ethylacetate 75 C, 10 min 2 h incubation enzyme linked immunosorbent assays 1 mL, 0.01 M HCl 60 C, 12 h
10
MTD, EDDP
50
MTD
20
MTD
10
COC, BZE, CE, EME, norCOC COC, BZE, EME, CE
20 50
COC, BZE
70
COC, BZE
50
Methanol
COC, BZE
20
Methanol
COC
20
Water, acetone
COC, anhydroEME, EME, CE COC
50
Dichlorometane, water, methanol Methanol
COC, EME, BZE, CE
50
COC, BZE
20–50
50
Methylene chloride, water, methanol Water, acetone, ultrasonic bath Water, acetone
Methanol
Dichloromethane, isopropanol, acetone Dichloromethane
Sample clean-up details
Derivatization Analytical techniques
Diethyl ether/ dichloromethane 20:80 v 1:v 1 Diethyl ether/ dichloromethane 20:80 v 1:v 1 Diethyl ether/ dichloromethane 20:80 v 1:v 1 Bond Elut Certify
MAE
IS
LOD (ng mg
1
LOQ (ng mg
)
References 1
)
LC-MS/MS
Diazepam-d5
[10]
LC-MS/MS
Diazepam-d5
[9]
LC-MS/MS
Diazepam-d5
0.03
UHPLC–MS– TOF
Lormetazepam
0.003–0.025
[64]
cutoff 100 pg mg
[129]
Immunoassay test
0.11
[80]
1
Automated SPE
ASPEC
GC–MS
MTD-d3
0.01; 0.06
0.05; 0.2
[128]
200 mL, 1 M HCl 60 C, 60 min 200 mL, 1 M HCl + 200 mg K2CO3 1 mL, 0.1 M HCl, 45 C overnight 1 mL, 0.1 M HCl, 45 C overnight 8 mL, 0.1 M HCl 45 C, 24 h
HS–SPME
101 micro PDMS 5 min 90 C MSTFA
GC–MS
MDPA
0.35
1.05
[91]
GC–MS
MDPA
0.05
0.16
[94]
TFAA/HFIP
GC-MS/MS
COC-d3
0.01
0.05
[126]
MSTFA
GC–MS
Scopolamine
0.04
[45]
1 mL, 0.1 M HCl, 45 C overnight 3 mL phosphate buffer 0.1 N pH 5, 45 C, 18 h 1 M HCl 60 C, 60 min 1 mL, 0.1 M HCl, 60 C overnight 2 mL, 0.1 M HCl, 40 C overnight 2 mL, 0.1 M HCl 50 C overnight 1 mL, 0.1 M HCl 45 C, 18 h
HS–SPME
SPE SPE
Clean screen SPE columns Bond Elut Certify
BSTFA/PFPA
GC–MS
COC-d3
SPE
CO2 modified with methanol (10%) Bond Elut Certify
MSTFA
GC–MS
BZE-d3
0.01–0.03
SPE
Bond Elut Certify
MSTFA/TCMS
GC–MS
COC-d3
0.05
HS–SPME
100 micro PDMS 5 min 90 C ASPEC
GC–MS
MDPA
0.35
1.05
[91]
GC-CI-MS/MS
COC-d3
0.005
0.05
[97]
GC–MS
COC-d3
GC–MS
MDA-d5,coc-d3, BE-d3,6-MAM-d6
SFE
Automated SPE LLE SPE
Dilution
MBTFA/ MSTFA + 1% TCMS 1:10 water
BZE-d3
[133]
0.02–0.09
[52] [46]
[47]
0.003
0.2
[103]
0.01
[40]
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
Cannabinoids
Compound
1
0.08
cutoff 500 pg mg
MDPA LC-MS/MS
Immunoassay test
HS–SPME
Bond Elut Certify SPE
10
50–200
10
COC
COC, BZE
COC CE
Water
10 COC, BZE, EME, CE
Water, acetone
1.5 mL phosphate buffer pH 5, 45 C, 18 h 2 h incubation enzyme linked immunosorbent assays 1 mL 0.1 M HCl 45 C overnight 200 mL, 1 M HCl + 200 mg K2CO3
5 COC
Methanol
0.1% SDS, water, dichloromethane
SPE
Bond Elut Certify
MSTFA
GC–MS
0.1 COC-d3
0.1 Mirtazapine
LCfluorescence detection LC-MS/MS
0.02 COC-d3, BZE-d3 20 COC, BZE
Dichloromethane, water, methanol
2 mL methanol, 1 mL, 0.1 M HCl, 65 C, 3 h 2 mL, 0.1 M HCl 45 C, 18 h
SPE
OASIS MCX 3 mL 60 mg waters
MSTFA/TCMS
LC-MS/MSSRM LC/MS3SRM GC–MS
Abbreviations: A, amphetamine; MA, methamphetamine; MDA, 3,4-methylenedioxyamphetamine; MDMA, 3,4-methylenedioxy-N-methylamphetamine; MDEA, 3,4-methylenedioxy-N-ethylamphetamine; THC, D(9)tetrahydrocannabinol; COC, cocaine; BZE, benzoylecgonine; EME, ecgonine methyl ester; CE, cocaethylene; MOR, morphine; COD, codeine; 6-MAM, 6-monoacteylmorphine; MTD, methadone; EDDP, 2-ethylidene-1,5dimethyl-3,3-diphenylpyrrolidine; MAE, microwave-assisted extraction.
[94] 0.25
[60]
[129]
[80] 0.34
[48] 0.3
0.05
[99]
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
13
3.1. Extraction with methanol Table 1 shows the methods described in the literature that use methanol in the extraction procedure. Methanol extraction has a wide spectrum of use and is compatible with testing procedures for almost all substances of abuse. The extraction generally consists of incubation in 1–2 mL of methanol in an ultrasonic bath for 5–18 h [28,30,38]. The extraction mechanism provides that the hydrophilic methanol penetrates into the hair, leading to swelling and the release of the substance via diffusion and to the dissolution of neutral and lipophilic compounds [20]. Ultrasonication causes particle size reduction as well as cell disruption in the hair structure and contributes to the extraction process. In this case, dissolution of the hair is incomplete and there is no hydrolysis of the analytes. In cases in which the substances are present in high concentrations, the methanol extracts could be injected directly into the GC–MS for analysis; these extracts, however, generally exhibit a high degree of contamination from the hair matrix, so a further purification step is recommended, in which liquid/liquid extraction (LLE) or solid phase extraction (SPE) is often performed. Another disadvantage of direct injection is that the recovery of the substance is often lower in comparison to LLE extraction [106]. Extraction with methanol has been widely used for the determination of amphetamines [26,30,38,41,63,95,105–108], benzodiazepines [30,37,71,102,107], cocaine [28,30,38,41,42, 63,107,110–113], opiates [28,30,38,41,42,63,107, 109,111,113], methadone [28,30,31,38,107,114] and cannabinoids [41,107,115,116]. A rapid LC-MS/MS method has been developed for the simultaneous determination of opiates, cocaine and benzoylecgonine. Aliquots of 20 mg of powdered hair samples were sonicated in methanol for 4 h at 40 C. The applicability of the method was demonstrated through the analysis of 79 real hair samples in which LOQs of 0.05 and 0.01 ng mg 1 were obtained for opiates and cocaine and its metabolites, respectively [113]. Kim et al. [95] proposed a rapid and simple method for the determination of amphetamines in hair samples. The method involves the incubation of the sample in ultrasound (10 mg) for 1 h at 50 C and GC–MS analysis after derivatization. LOQs equal to 0.1 ng mg 1 for amphetamine and methamphetamine and 0.05 ng mg 1 for 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) were obtained. An automated screening method has recently been developed. This method uses the LC–TOFMS technique for the identification and simultaneous quantification of 30 substances of abuse, including opiates, cocaine and its main metabolites, cannabinoids and amphetamines [107]. In this study, three sample preparation procedures were evaluated: extraction with methanol, acid extraction and alkaline digestion. The best results, in terms of extract recovery and cleanness, were obtained using the extraction of 20 mg of hair with methanol and sonication in 4 mL of methanol for 8 h at 50 C. LOQ values were obtained in the range of 0.015– 0.15 ng mg 1[107]. Extraction with methanol in basic conditions has also been proposed for the determination of amphetamines [59,92] with an LOQ of 0.14 ng mg 1, benzodiazepines [78,79,100,117,118] with LOQs of 0.23–20 ng mg 1 and cannabinoids [115] with an LOQ of 0.1 pg mg 1. More details are reported in Table 1 (basic methanol). Rust et al. [117] proposed a method for the determination and quantification of 21 benzodiazepines and ‘Z-drugs’, which involves extraction via micropulverisation of 30 mg of sample in the presence of 1.5 mL of methanol for 90 min. A second extraction step is then carried out by stirring for another 90 min under acidic conditions, using a buffer solution of 5 mM ammonium formate at pH 3.5 and methanol (1:1). The LC-MS/MS analysis was carried out
14
Table 4 Extraction with solvent mixtures. Class
Compound
Methadone
Amphetamines
LOD (ng mg
)
LOQ (ng mg
20 mL acetonitrile, 20 mL TFA 1 M, 145 mL water
LC–HRMS
Nordiazepam-d5
0.03–0.15
0.1–0.5
[19]
0.5 mL methanol: acetonitrile:2 mM ammonium formate (25:25:50) 37 C, 18 h
LC–QTOF– MS
0.003–0.015 7Aminoflunitrazepamd7
0.006–0.021
[93]
Methanol
methanol:acetonitrile: PTFE ammonium formate filter (2 mM, 8% acetonitrile pH 5.3) 37 C overnight
UPLC– TOF–MS
Diazepam-d5
0.05
[50]
2-Propanol, 0.01M phospahte buffer, 2propanol
0.45–mL acetonitrile:25 mM formic acid (5:95), 37 C, 18 h 0.5 mL acetonitrile: methanol:20 mM formate buffer pH 3 (10:10:80) 37 C, 18 h methanol: acetonitrile:20 mM ammonium formate (25:25:50) 2 h 20 mL acetonitrile, 20 mL TFA 1 M, 145 mL water
LC-MS/MS
7Aminoflunitrazepamd7
0.005– 0.0125
[75]
LC-MS/MS
Diazepam-d5
0.017–0.07
0.058–0.232
[130]
NanoHPLCChip-MS/ MS LC–HRMS
Methadone-d3
0.1– 0.75 pg mg
0.2– 1.25 pg mg
[77]
Washing
2.5
20
10% aqueous solution of SDS, water, acetone Water, acetone
10
20
Diazepam, 7-aminoflunitrazepam
20–50
MTD
2
MTD, EDDP
2.5
MTD, EDDP
20
MTD
20
A, MA, MDA, MDEA, MDMA
2
0,1% SDS deionized water acetone 10% aqueous solution of SDS, water, acetone Water, acetone
2-Propanol, 0.01 M phospahte buffer, 2propanol 0.1% SDS deionized water acetone
A, MA, MDA, MDEA, MDMA
0.2
A, MA, MDA, MDMA, MDEA
2.5
A, MA, MDA, MDEA, MDMA
20
0.1% SDS, water, methanol 10% aqueous solution of SDS, water, acetone Water, acetone
A, MA,MDEA, MDMA, MDA
10
Methanol
Extraction procedure
Sample cleanup type
No
0.5 mL methanol: acetonitrile:2 mM ammonium formate (25:25:50) 37 C, 18 h 0.45 mL acetonitrile:25 mM formic acid (5:95), 37 C, 18 h Methanol: acetonitrile:20 mM ammonium formate (25:25:50) 2 h Micropulverized extraction 20 mL acetonitrile, 20 mL TFA 1 M, 145 mL water 0.5 mL methanol: acetonitrile:2 mM ammonium formate (25:25:50) 37 C, 18 h Methanol:acetonitrile: ammonium formate
No
Sample cleanup details
No
0.01–0.10
1
References 1
)
1
Cocaine-d3
0.03–0.15
0.1–0.5
[19]
LC–QTOF– MS
EDDP-d3
0.001
0.003
[93]
LC-MS/MS
Morphine-d3
0.0125
[75]
NanoHPLCChip-MS/ MS LC-MS/MS
A-d8, MA-d5, MDAd5, MDMA-d5, MDEA-d5 Methamphetamined5 MDPA
LC–QTOF– MS
UPLC– TOF–MS
LC–HRMS
PTFE filter
1
0.1– 0.75 pg mg
1
0.2– 1.25 pg mg
[77] 1
0.1
[66]
0.03–0.15
0.1–0.5
[19]
Amphetamine-d5
0.001–0.003
0.002–0.003
[93]
Amphetamine-d5
0.01–0.10
0.05–2
[50]
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
Benzodiazepines 7-Aminoclonazepam, 7-aminoflunitrazepam, oxazepam, diazepam, alprazolam, lorazepam, nordiazepam 7-Aminoflunitrazepam, bromazepam, alprazolam, clobazam, clonazepam, 7aminiclonazepam, diazepam, lormetazepam, midazolam, nordiazepam, oxazepam, temazepam 7-Aminoflunitrazepam, bromazepam, alprazolam, clobazam, clonazepam, 7aminiclonazepam, diazepam, lormetazepam, midazolam, nordiazepam, oxazepam, temazepam 7-Aminonitrazepam, 7-aminoclonazepam, 7aminoflunitrazepam, oxazepam, diazepam, alprazolam
Analytical IS techniques
Sample amount (mg)
Cocaine
20
A, MA
2
A, MA A, MA, MDA, MDMA
10 20–50
A, MA, MDA, MDMA,MDEA
100
COC, BZE, CE, norCOC
2
COC, BZE
0.2
COC, BZE
2.5
COC, BZE, CE
20
COC, BZE
10
COC
2.5
COC, BZE, CE
50
COC, BZE
20
COC, BZE
20–50
COC, BZE, norCOC
100
MOR, COD, 6-MAM
2
MOR, COD, 6-MAM
2.5
COD, MOR, 6-MAM
20
2-Propanol, 0.01 M phospahte buffer, 2propanol
LC-MS/MS
Amphetamine-d11
0.005–0.025
[75]
2 mL chlorobutane
LC-MS/MS
0.04
[109]
MEPS 0.5 mL acetonitrile: methanol:20 mM formate buffer pH 3 (10:10:80) 37 C, 18 h PLE
GC–MS LC-MS/MS
Amphetamine-d5, methamphetamined5 A-d5, MA-d5 Amphetamine-d5
Isopropanol, dichloromethane Methanol: 0,1% SDS deionized water acetonitrile:20 mM ammonium formate acetone (25:25:50) 2 h 0,1% SDS, water, Micropulverized methanol extraction 20 mL acetonitrile, 20 mL 10% aqueous TFA 1 M, 145 mL water solution of SDS, water, acetone Water, acetone 0.5 mL methano: acetonitrile:2 mM ammonium formate (25:25:50) 37 C, 18 h Methanol Methanol:acetonitrile: ammonium formate (2 mM, 8% acetonitrile pH 5.3) 37 C overnight Water, acetonitrile 1 M TFA (80:10:10) Tween 80, water 0.5 mL methanol, 11 mL dichlorometane 60 C, 9 min 0.45 mL 2-Propanol, acetonitrile:25 mM 0.01 M formic acid (5:95), 37 C, phospahte buffer, 218 h propanol 0.5 mL acetonitrile: methanol:20 mM formate buffer pH 3 (10:10:80) 37 C, 18 h Isopropanol, PLE dichloromethane Methanol: 0.1% SDS deionized water acetonitrile:20 mM ammonium formate acetone (25:25:50) 2 h 20 mL acetonitrile, 20 mL 10% aqueous TFA 1 M, 145 mL water solution of SDS, water, acetone Water, acetone 0.5 mL methanol/ acetonitrile/2 mM
SPE No
LC-MS/MS No
PTFE filter
NanoHPLCChip-MS/ MS LC-MS/MS
Methamphetamined9 COC-d3, CE-d3, norCOC-d3, BZE-d3
4– 33 pg mg
0.20 13– 110 pg mg
1
5 0.1– 0.75 pg mg
1
No
[77] 1
0.1
[66]
Benzoylecgonine-d3
0.03–0.15
0.1–0.5
[19]
LC–QTOF– MS
Benzoylecgonine-d3
0.001
0.002–0.003
[93]
UPLC– TOF–MS
Amphetamine-d5
0.01–0.03
0.05
[50]
0.1
[132]
LC–UV
No
0.2– 1.25 pg mg
[81]
LC–HRMS
MALDI MS
SPE
[131] [130] 1
0.2
[108]
0.0025– 0.0125
[75]
0.01–0.016
[130]
12.5; 1.25
[81]
LC-MS/MS
Morphine-d3
LC-MS/MS
Cocaine-d3
LC-MS/MS
Cocaine-d3
nanoHPLCChip-MS/ MS LC–HRMS
MOR-d6, COD-d6, 6-MAM-d3
0.1– 0.75 pg mg
Cocaine-d3
0.03–0.15
0.1–0.5
[19]
LC-QTOFMS
6-Acetylmorphined3
0.001
0.003
[93]
0.003–0.005
1
0.2– 1.25 pg mg
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
Opiates
A, MA,MDA, MDMA
(2 mM, 8% acetonitrile pH 5.3) 37 C overnight 0.45 mL acetonitrile:25 mM formic acid (5:95), 37 C, 18 h
[77] 1
15
[75]
[130]
[81]
0.005– 0.0125
0.018–0.083
5 Morphine-d3
Morphine-d3 LC-MS/MS
LC-MS/MS
Morphine-d3 LC-MS/MS
LC–UV
SPE Isopropanol, dichloromethane
0.5 mL acetonitrile: methanol:20 mM formate buffer pH 3 (10:10:80) 37 C, 18 h PLE
20
20–50
100
MOR, COD, 6-MAM
MOR, 6-MAM, COD, ethylMOR
MOR, 6-MAM, COD
2-Propanol, 0.01 M phospahte buffer, 2propanol
50 COD, MOR, 6-MAM
Tween 80, water
10 COD, MOR, 6-MAM
Methanol
ammonium formate (25:25:50) 37 C, 18 h Methanol:acetonitrile: PTFE ammonium formate filter (2 mM, 8% acetonitrile pH 5.3) 37 C overnight 0.5 mL methanol, 11 mL dichlorometane 60 C, 9 min 0.45 mL acetonitrile:25 mM formic acid (5:95), 37 C, 18 h
Abbreviations: A, amphetamine; MA, methamphetamine; MDA, 3,4-methylenedioxyamphetamine; MDMA, 3,4-methylenedioxy-N-methylamphetamine; MDEA, 3,4-methylenedioxy-N-ethylamphetamine; COC, cocaine; BZE, benzoylecgonine; CE, cocaethylene; MOR, morphine; COD, codeine; 6-MAM, 6-monoacteylmorphine; MTD, methadone; EDDP, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine.
[108] 0.2
0.004–0.025
[50] 0.01–0.03 Methadone-d3 UPLC-TOFMS
) 1
LOQ (ng mg ) 1
LOD (ng mg Sample amount (mg) Compound Class
Table 4 (Continued)
Washing
Extraction procedure
Sample cleanup type
Sample cleanup details
Analytical IS techniques
0.05–0.50
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27 References
16
in a QTRAP system without further purification of the sample. LOQ values were obtained in the range of 0.6–16 pg mg 1. With methanol under acidic conditions, amphetamines, benzodiazepines and opiates were also extracted with good efficiency prior to derivatization and GC–MS analysis [25,43,119–122], LC–MS [65], HPLC-fluorescence liquid chromatography [68,70,123], LCMS/MS [73], GC/MS/MS [76] or GC–HRMS [124]. 3.2. Extraction with acetonitrile Acetonitrile is another organic solvent sometimes employed for the extraction of substances of abuse from hair [27,125]. Table 2 shows the methods proposed in the literature using acetonitrile in the extraction procedure. Lendoiro et al. [27] proposed a procedure for screening and confirmation of 35 licit and illicit drugs and metabolites, including opiates, amphetamines, cocaine, delta-9-tetrahydrocannabinol (THC), benzodiazepines and some antidepressants. For the incubation step, various solvents were tested in acidic, basic and organic solvent conditions (methanol and acetonitrile). In a basic environment, partial hydrolysis of some substances, such as cocaine, benzoylecgonine and 6-monoacetylmorphine, occurs, while in an acidic environment, THC is not extracted. In the author’s opinion, using methanol, good extraction yields were obtained for all compounds; however, even after cleanup through LLE and SPE, the extracts obtained, were too dirty for LC-MS/MS analysis. The best results were obtained by incubation of 50 mg of powdered hair with 2 mL of acetonitrile for 12 h at 50 C in a thermostated bath, which resulted in excellent recovery of all analytes and clean extracts after cleanup through LLE and SPE. LOQ values at least equal to those proposed by the Society of Hair Testing (SoHT) guidelines were obtained for opiates (0.2 ng mg 1) and for cocaine and its major metabolite, benzoylecgonine (respectively, 0.5 ng mg 1 and 0.05 ng mg 1), for amphetamines (0.2 ng mg 1), and for THC (0.1 ng mg 1). The method proposed by Lendoiro et al. is particularly interesting in that a single procedure with the same LC-MS/MS method allows the extraction and analysis of 35 analytes, including tetrahydrocannabinol (THC), which is generally analyzed separately by GC–MS. However, the cleanup procedure is rather onerous, since the extracts are first purified through an LLE step and then through an SPE step. Acetonitrile was also used for the selective extraction of cocaine and benzoylecgonine from hair by Thibert et al. [125]. Aliquots of 50 mg of sample were subjected to sonication for 2 h in the presence of 2 mL of acetonitrile; the purification of the sample was then achieved through percolation of the extracts through a synthesized molecularly imprinted polymer (MIP). A recovery of nearly 80% and LOQ values of 0.07 ng mg 1 and 0.04 ng mg 1 for cocaine and benzoylecgonine, respectively, were obtained. Therefore, acetonitrile, although still not widely used, appears to be a useful solvent in the extraction of drugs from hair, applicable to a wide range of analytes, and with good extraction yields. 3.3. Extraction by aqueous or buffer solutions In Table 3 are reported the methods proposed in the literature that use aqueous solutions or buffer solutions in the extraction procedures. The basic substances (opiates, cocaine and its metabolites, amphetamines and methadone) are effectively extracted through the use of phosphate buffer (pH5 or pH8) or by aqueous HCl 0.1 M, due to protonation of the nitrogen atom(s) present in the molecules and an increase in their aqueous solubility.
Table 5 Digestion with aqueous NaOH. Class
amphetamines
Derivatization
0.5 mL, 1.5 M LLE NaOH
2 mL cyclohexane
PFOC
1 mL, 1 M NaOH
50 mL chloroform, solid KCl ISOLUTE HCX-5
A, MA,MDA, MDMA
10
A, MA,MDA, MDMA
20
2 mL isopropanol, 1 mL, 0.01 M phosphate buffer 3 times Detergent, distilled water
A, MA,MDA
150– 250
Ethanol
A, MA,MDA, MDMA,MDEA, MBDB MA
20
Ethanol, dichlorometane
2 mL, 1 M SPE NaOH 100 C, 1 h 1 M NaOH LLE 80 C, 15 min
A, MA,MDA, MDMA,MDEA
50
A, MA,MDA, MDMA,MDEA
50
A, MA,MDA, MDMA,MDEA
1% SDS, methanol
10
5–30
A, MDMA,MDEA
Dichloromethane, redistilled water, methanol Deionized water, acetone Water, petroleum ether, dichloromethane
Water, acetone
Dichlorometane
A, MA, MDMA, MDA, MDEA
10
Dichlorometane
A, MA, MDMA, MDA
50
Dichlorometane
150– 250
Ethanol
benzodiazepines alprazolam
720 aminoclonazepam
Dichloromethane
THC-COOH
30
THC-COOH
20
Water, acetone, methanol, dichloromethane, phosphate buffer 1 mL methanol
Extraction procedure
Sample cleanup type
LLE
0.5 mL, 1 M NaOH 70 C, 30 min 1 mL NaOH 40 C, 1 h
SPME
1 mL, 1 M NaOH
LLE
NaOH 70 C, 20 min 1 mL, 10 M NaOH
SPME HS– SPME
1 M NaOH 70 C 1 M NaOH 100 C, 30 min 1 mL, 1 N NaOH 95 C, 10 min 1 M NaOH 37 C overnight 1 M NaOH 70 C, 15 min
HS– SPME SPE
LLE
Analytical IS techniques
LOD (ng mg
GC–MS
A-d5
0.07–0.14
0.24–0.46
[74]
GC–MS
2-Methylbenzylamine
0.02
0.05
[137]
LC/TOFMS
Dibenzin
A-d5
n-Hexane:ethyl acetate 2:1 v 1:v 1
5 mL methylene chloride/ isopropanol 2 mL 1chlorobutane
1
LOQ (ng mg
)
References 1
)
[61]
0.0061
0.0147
[83]
Trufluoroacetic GC–MS anhydride TFAA
N-n-Buthylaniline
PFPA 65 C, 20 min
GC–MS
A-d5
0.007–0.045
0.023–0.151
[135]
LC–APCI– MS
A-d5
0.10
0.15
[101]
GC–MS
MPDA
3.14
9.43
[89]
MBTFA
GC–MS
A-d5
0.01–0.17
0.03–0.54
[82]
HFB-Cl
GC–MS
MA-d5
00:01
HFBP-Cl
GC–MS
A-d5, MA-d5, MDA- 0.0021–0.0459 d5, MDMA-d5, MDEA-d5 0.1
GC–MS
[69]
[134]
SPE
MBTFA
GC–MS
HF– LPME
TFAA: ethylacetate 50:50 v 1:v 1
GC–MS
A-d5, MA-d8, MDA- 0.03–0.08 d5, MDMA-d5, MDEA-d5 A-d5, MDMA-d5
ISOLUTE HCX-5
LC/TOFMS
Dibenzin
2 mL dichloromethane
LC-MS/MS
1 mL, 0.1 M SPE NaOH 100 C, 30 min LLE 1 mL NaOH 85 C, 30 min
Waters, Milford
LC/ESI LC/ SACI-ESIMS MS/MS
2 pg mg 7Aminoclonazepamd4 THC-COOH-d3
PFPA/PFPOH
GC/MS/ MS-NCI
THC-COOH-d3
[96]
[29]
[39]
0.05
[22]
[61]
1
0.025 pg mg
>10 pg mg
1
[32]
[139]
1
[53] 17
SPE 2 mL, 1 M NaOH, 100 C, 1 h 0.1 N NaOH LLE 95 C, 15 min
0.0043–0.0918
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
Washing
MDA, MDMA, MDE,MBDB A, MA,MDA, MDMA,MDEA, BDB, MBDB A, MA
cannabinoids
Sample clean-up details
Sample amount (mg)
Compound
18
Table 5 (Continued) Class
Compound
THC,THC-COOH
Sample amount (mg)
20
THC-COOH
Washing
Extraction procedure
Sample cleanup type
1 mL NaOH LLE 85 C, 30 min
1 mL methanol
1 mL NaOH LLE 85 C, 30 min 1 mL NaOH 1 M, 10 min, 95 C 1 mL, 1 M NaOH 90 C, 15 min 1 mL, 1 M NaOH 85 C, 15 min 1 mL, 1 M NaOH 0.5 g NaCl 1 mL, 1 M NaOH 95 C, 30 min 0.5 mL, 1nM NaOH 80 C, 20 min 1 mL, 0.1 N NaOH 100 C, 30 min 1 M NaOH 95 C, 10 min
LLE
THC, THC-COOH
30–50
Water, petrol, ether, acetone
THC, CBD, CBN
10
THC, CBD, CBN
10
THC
10
Petroleum ether, deionized water, dichloromethane Petroleum ether, deionized water, dichloromethane Water, acetone, ultrasonic bath
THC-COOH
25
Isopropyl alcohol
THC, CBD, CBN
15–30
Deionized water, acetone
THC, CBD, CBN
50
Dichloromethane
THC, CBD, CBN
50
Isopropyl alcohol
THC-COOH
25
Isopropyl alcohol
1 M NaOH LLE 30 C, 10 min
THC, CBD, CBN
10
1 mL NaOH
TNC, CBD, CBN
10
5 mL deionised water, petroleum ether, dichloromethane 5 mL deionised water, petroleum ether, dichloromethane Dichlorometane
1 mL, 1 M NaOH
THC, CBD, CBN
THC-COOH
20
1.5 mL dichlorometane
THC-COOH THC,THC-COOH
20
KH2PO4 1 M, water, methanol
1 mL, 1 N NaOH 95 C, 10 min 1 mL, 1 N NaOH 80 C, 30 min 2 M NaOH 95 C
SPME
n-Hexane:ethyl acetate 9:1 v 1:v 1 n-Hexane:ethyl acetate 9:1 v 1:v 1 n-Hexane:ethyl acetate 9:1 v 1:v 1 n-Hexane:ethyl acetate 9:1 v 1:v 1 PDMS fiber
Derivatization
Analytical IS techniques
LOD (ng mg
PFPA/PFPOH
GC/MS/ MS-NCI
THC-d3, THCCOOH-d3
THC:2.5 pg mg 1 THCCOOH:0.025 pg mg
PFPA/PFPOH
GC/MS/ MS-NCI
THC-COOH-d3
MSTFA
GC–MS
THC-D3
LLE
n-Hexane-ethyl acetate 9:1 v 1:v 1
LOQ (ng mg
)
1
References 1
)
THC:7.5 pg mg 1 THCCOOH:0.05 pg mg
[54] 1
[55]
0.02
0.05
[84]
GC-MS/MS THC-d3
0.031
0.062
[88]
GC-MS/MS THC-d3
0.015
0.02
[87]
MSTFA
GC–MS
0.01
0.02
[94]
PFPOH/PFPA
GC-MS/MS THC-COOH-d9
0.02 pg mg
GC–MS
THC-COOH-d3
0.012
THC-COOH-d3
0.025
[35]
[56]
HF– LPME SFME
1
SPME
THC-d8
1
1
0.05 pg mg
0.037
[58]
[90]
LLE
n-Hexane
GC/MS
LLE
n-Hexane-ethyl acetate 75:25 v 1:v 1 n-Hexane-ethyl acetate 9:1 v 1:v 1
GC–MS
0.006
PFPOH/PFPA
GC-MS/MS THC-COOH-d9
0.015 pg mg
SPME
MSTFA
GC–MS
THC-COOH-d3
0.05–0.14
0.27–0.51
[86]
HS– SPDE
MSTFA
GC–MS
THC-d3
0.14
0.45
[85]
GC–MS
SPE
LLE
n-Hexane-ethyl acetate 75:25 v 1:v 1 Hexane/ ethylacetate Hexane/ ethylacetate
TFAA/HFIP
TMSI/HFIP/ PFPA
GC–MS
1
1
0.05 pg mg
0.1
THC-COOH-d3
0.3 pg mg
[57]
[29]
1
GC–MS
0.0003
GC-MS/MS THC-d3, THCCOOH-d3
0.001–0.0001
0.4 pg mg
0.0011
1
[44]
[138] [140]
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
1 mL methanol
Sample clean-up details
metadone
LLE
50
THC-COOH
20
Dichloromethane
2 N NaOH
SPE
THC-COOH
20
Methanol
LLE
THC-COOH
20
Dichloromethane
THC-COOH
50
Dichloromethane
MTD
150– 250
Ethanol
1 mL, 1 M NaOH 85 C, 30 min 1 mL, 1 M NaOH 80 C, 30 min 1 mL, 1 M NaOH 80 C, 1h 2 mL, 1 M NaOH 100 C, 1 h 1 mL, 1 M NaOH 0.5 g NaCl 110 C, 20 min 1 mL, 1 M NaOH 50 C, 45 min 2 mL, 1 M NaOH 100 C, 1 h
MTD, EDDP
10
COD
150– 250
Dichloromethane, deionized water, methanol Ethanol
SPE
n-Hexane-ethyl acetate 9:1 v 1:v 1 n-Hexane-ethyl acetate 75:25 v 1:v 1 n-Hexane-ethyl acetate 9:1 v 1:v 1 n-Hexane-ethyl acetate 75:25 v 1:v 1 Heptane/ ethylacetate 9:1 v 1:v 1 ISOLUTE HCX-5
HS– SPME
65 micro PDMS DVB 20 min
SPE
LLE
SPE
SPE
ISOLUTE HCX-5
BSTFA
GC-MS/MS THC-COOH-d3
TFAA/HFIP
GC-MS/MS THC-COOH-d3
PFPOH/PFPA
GC-MS/MS THC-COOH-d3
TFAA/HFIP
GC–MS
PFPOH/PFPA
GC-MS/MS THC-COOH-d3
[141]
0.025 pg mg
1
0.05 pg mg
1
[24]
0.05 pg mg
1
[51]
THC-COOH-d3
LC/TOFMS
Dibenzin
GC–MS
MTD-d9
GC–MS
MTD-d3
LC/TOFMS
Dibenzin
[23]
0.05
0.1
[34]
[61]
0.03
[142]
0.1
[98]
[61]
Abbreviations: A, amphetamine; MA, methamphetamine; MDA, 3,4-methylenedioxyamphetamine; MDMA, 3,4-methylenedioxy-N-methylamphetamine; MDEA, 3,4-methylenedioxy-N-ethylamphetamine; THC, D(9)tetrahydrocannabinol; CBD, cannabidiol; CBN, cannabinol; THC-COOH, 11-nor-9-carboxy-D9-tetrahydrocannabinol; COC, cocaine; BZE, benzoylecgonine; EME, ecgonine methyl ester; CE, cocaethylene; MBDB, N-methyl-1(1,3-benzodioxol-5-yl)-2-butanamine; BDB, 3,4-(methylenedioxyphenyl)-2-butanamine; COD, codeine; MTD, methadone; EDDP, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine; HFLPME, hallow-fiber liquid-phase micro extraction; TFAA, trifluoroacetic anhydride; HFIP, 1.1,1,3,3,3-hexafluoro-2 propanol.
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
THC-COOH
MTD, EDDP
opiates
1 mL, 1 M NaOH 75 C, 30 min NaOH
19
20
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
Several analytical methods, based on extraction in aqueous acid, have been described for the determination of opiates, cocaine and its metabolites [40,45–48,52,60,91,93,97,126], amphetamines [60,91,94,104,127] and methadone [91,94,128]. One frequently occurring disadvantage of this approach is the partial hydrolysis of cocaine to benzoylecgonine and of 6-acetylmorphine to morphine. Heroin (diacetylmorphine) can never be determined in aqueous extracts, even if it is well settled in the hair. The main advantage of acid extraction is the possibility of simultaneous analysis of opiates, cocaine, amphetamines and other substances of wide consumption [49,67,80,103,129] and benzodiazepines, which can also be extracted [8,33,36,62,64,80, 103,106] by the same approach. Cordero et al. [103] proposed a method for the simultaneous determination of opiates, cocaine and its metabolites, amphetamines, and diazepam and its metabolite nordiazepam, through a GC–MS method with derivatization after extraction of hair in 2 mL of HCl 0.1 M and overnight incubation at 50 C. Extract purification was performed through the SPE technique using mixed-mode extraction columns. LOQ values of 5 ng mg 1 for amphetamine and 10 ng mg 1 for the other substances were obtained. Recently, Guthery et al. [49] applied a two-dimensional GC–TOFMS (GCGC–TOFMS) for the qualitative determination of xenobiotics in hair. The extraction was performed using 1 mL HCl 0.1 M for 16 h at 37 C. The target analytes were opiates, amphetamines and methadone, but due to high resolution mass spectrometry, the GCGC–TOFMS analysis was able to identify several substances, such as metabolites and impurities, which were not included among the analysis targets; these components were identified by comparison with mass spectra in the database library. Miller et al. [80] proposed a method for the simultaneous determination and quantification of cocaine and its metabolite benzoylecgonine, opiates, amphetamines, and diazepam and its metabolites in the keratinic matrix using the LC-MS/MS technique, applying a single extraction procedure. Phosphate buffer with a pH of 5 was chosen as the ideal medium for the incubation, since better stability of cocaine and 6-MAM, as well as faster sample preparation were observed. The recovery of the analytes and limits of detection/quantification were evaluated by two different SPE methods: the SPE Clean Screen method resulted in the lowest LODs and LOQs for most analytes. Villain et al. [33] proposed an alternate screening method for 16 benzodiazepines, which involved the incubation of 20 mg of sample using phosphate buffer at basic pH (8.4), purification by LLE and subsequent LC-MS/MS analysis. Quite low LOQs ranging between 0.5 and 5 pg mg 1, were obtained using this approach. Wietecha-Posluszny et al. [64] validated a rapid method for the preparation of hair samples using microwave irradiation for the determination of six benzodiazepines. In this case, borate buffer (pH 9) and ethylacetate were added to 45 mg of hair sample. UPLC–MS–TOF analysis was performed. An LOD in the range of 0.003–0.025 ng/mg was achieved. 3.4. Extraction with solvent mixtures Table 4 summarizes the methods proposed in the literature that employ extraction with solvent mixtures for the analysis of benzodiazepines [19,50,75,93], methadone [19,75,77,93], amphetamines [19,50,66,75,77,81,93,109,129–131], cocaine [19,50, 66,75,77,81,93,108,129] and opiates [19,50,75,77,81,93,108,129]. The procedures so far described for analyte extraction are generally lengthy and the resulting solutions contain interfering species of low molecular weight that render direct chromatographic analysis problematic and therefore require that the sample undergoes additional purification steps (SPE or LLE), which
further extend the analysis time. In addition, those procedures may cause degradation of certain analytes, such as cocaine, heroin and monoacetylmorphine. Extraction in an aqueous environment at neutral or acid pH has the disadvantage of excluding the lipophilic species [61]. It was demonstrated that swelling the hair sample with water or other hydrophilic solvents, such as methanol, is an essential pre-requisite for high-yield extraction. However, methanol, while a non-reactive and universal extraction solvent, has the disadvantage of obtaining a high degree of contamination on the part of the constituents of the matrix and often results in low-yield extraction. As an alternative, Kronstrand et al. [130] developed a simple extraction method for different groups of substances based on direct dissolution of the sample in the mobile LC phase—a mixture of acetonitrile:methanol:ammonium formate buffer 20 mM, pH 3.0 (10:10:80, v 1:v 1:v 1), for 18 h at 37 C. Hegstad et al. [75], based on the method presented by Kronstrand et al. [130], proposed the following procedure: 0.45 mL of acetonitrile/25 mM of formic acid (5:95, v 1:v 1) for 18 h at 37 C. This approach was optimized by Nielsen et al. [50] using a mixture of methanol, acetonitrile and 2 mM of ammonium formate containing 8% acetonitrile (pH 5.3) in the ratio of 25:25:50 (v 1:v 1:v 1) for 18 h at 37 C. In order to increase the speed and simplicity of the analysis of the keratinic matrix, Miyaguchi et al. [66,109,131] proposed an approach for hair sample preparation—a method involving micropulverisation and simultaneous extraction for amphetamines, followed by direct injection of the filtered suspension via LC-MS/MS analysis. With this approach, the amount of sample was reduced from 10–50 mg to 2 mg [109], downto 0.2 mg [66]. The original solvent for extractionmicropulverisation was 0.1 mol L 1 trifluoroacetic acid (TFA) in 10% acetonitrile [109]. In addition, a saline solution of phosphate buffer [131] was tested as an extraction solvent for the amphetamine group; in the last work, 0.1 mol L 1 of ammonium formate (pH 3.5) with formic acid was used [66]. A pressurized-liquid extraction procedure, which uses solvents at high temperatures and pressure to extract analytes from solid or semisolid samples, was used by Sergi et al. [81] for quantitative recovery of amphetamines, cocaine and its metabolites and opiates. In a single extraction step, 100 mg of hair were extracted using water:methanol (80:20, v 1:v 1) as the extraction solvent. A rapid extraction method for the determination of opiates, and cocaine and its metabolites, based on the use of microwaves, was proposed by Fernàndez et al. [108]. In this case, 50 mg aliquots of sample are extracted by means of microwaves in the presence of a mixture of methanol and dichloromethane. After filtration and evaporation of the organic solvent, the extract is reconstituted using the mobile phase for direct injection in an HPLC system with UV photodiode array detection. Vogliardi et al. [132] proposed a new screening method for cocaine in hair samples based on matrix-assisted laser desorption/ ionisation (MALDI) through the rapid extraction of 2.5 mg of pulverized sample in the presence of (acetonitrile:TFA:water 10:10: 80, v 1:v 1:v 1). Favretto et al. [19] applied the same extraction mixture in a simultaneous pulverizing/extraction procedure that necessitates no cleanup of the extract for the simultaneous determination of 28 analytes belonging to six different classes (amphetamines, cocaine, opioids, benzodiazepines, antidepressants and hallucinogens). The procedure, whichreduces sample preparation time to less than 40 min, was validated on 2.5-mg hair samples, reaching LLOQ values as low as 0.1–0.5 ng/mg, depending on the compound. Broecker et al. [93] optimized a procedure for the extraction of 20 mg of sample by incubation for 18 h with methanol/acetonitrile/ water/ammonium formateat 37 C.
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
A rapid method of sample preparation for the simultaneous determination of cocaine and metabolites, opiates, amphetamines and methadone was recently proposed by Zhu et al. [77]. Aliquots of 2 mg of sample wereextracted with a mixture consisting of methanol:acetonitrile:ammonium formate 20 mM (25:25:50, v 1:v 1:v 1). After centrifugation and evaporation of the supernatant, the extract was reconstituted for direct injection into a nanoHPLC-Chip-MS/MS system. Supercritical fluid extraction (SFE), which exploits CO2 in its supercritical state, was also proposed for the preparation of hair sample. The use of supercritical fluids wasapplied to the extraction due to their unique properties of low viscosity and rapid extraction with high mobility [133]. The methanolic extracts were treated at 300 bar and 50–70 C with CO2. Modifiers such as ethyl acetate, chloroform or isopropanol can be used to improve the CO2 as solvent. Despite the advantages of rapid extraction, a high yield, miniaturization and automation, this method is rarely used because of its high cost. 3.5. Digestion with aqueous NaOH Table 5 summarizes the methods proposed in the literature that involve extraction with NaOH. For substances that are stable in alkaline conditions, an advantageous method for disgregation/extraction from hair consists of digestion in an aqueous solution of NaOH followed by solvent. Under these conditions, there is complete dissolution of the hair by NaOH, but hydrolysis of monoacetylmorphine, heroin and cocaine also occurs. The extraction in a basic environment is, however, particularly advantageous for amphetamines [22,29,39,61,69,74,82,83,89,96,101,134–137] and cannabinoids [23,24,29,34,35,44,51,53–88,90,94,138–141]. This approach has also been reported for the extraction of benzodiazepines [13,116], codeine [61] and methadone [61,98,142]. In most cases, hair samples are incubated with 1–2 mL of NaOH 1 M or 10 M, for 10–60 min at temperatures between 70 C and 100 C. In the work proposed by Emìdio et al. [87] for the analysis of cannabinoids in hair, digestion was carried out on 10 mg of sample using 1 mL NaOH 1 M at 90 C for 15 min. The extraction of the analytes from the matrix was obtained by headspace solid-phase microextraction (HS-SPME) followed by GC–MS analysis. In this case, particularly low LOQs of 0.007 ng mg 1, 0.011 ng mg 1 and 0.031 ng mg 1 for cannabidiol (CBD), cannabinol (CBN) and THC, respectively, were obtained. Conti et al. [138] recently developed a new method based on surface-activated chemical ionization (SACI) combined with electrospray ionization (ESI) and mass spectrometry (ESI-SACIMS) in order to improve the detection of 11-nor-9-carboxy-delta9-tetrahydrocannabinol (THC-COOH). Aliquots of 30 mg of sample were hydrolysed using 1 mL NaOH 0.1 M at 100 C for 30 min. The extracts obtained were then purified by SPE prior to LC/MS-MS, LC/ SACI-ESI-MS and MS/MS analysis conducted using the Orbitrap analyser, a linear ion trap analyser, and a triple quadrupole mass spectrometer. A qualitative method for screening for basic substances using LC coupled with TOF mass spectrometry was proposed by Pelander et al. [61]. Through the analysis of 32 hair samples from deceased drug addicts, 35 different substances were detected, including amphetamines, opiates, benzodiazepines and methadone. Relatively high amounts of hair (150–250 mg) were digested by the addition of 2 mL NaOH 1 M at 100 C for 1 h; the samples were purified by mixed-mode SPE using ISOLUTE HCX-5 cartridges. Recently, Barroso et al. [98] developed and validated a rapid method for the determination of methadone and its major metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine
21
(EDDP). The analytes were extracted from the matrix after a short incubation in an alkaline environment of 10 mg of sample with 1 mL NaOH 1 M at 50 C for 45 min. The extracts were then purified by SPE using mixed-mode cartridges. An LOQ of 0.1 ng mg 1 was achieved for both compounds. 3.6. Enzymatic digestion This method is sometimes used for the extraction of drugs from hair samples. Enzymatic solutions are used, buffered to an optimum pH for the hydrolytic activity of the enzyme with which the sample is broken down by incubation at 40–60 C for 6–24 h. The use of ultrasound and matrix solid phase dispersion for assisting the enzymatic hydrolysis process leads to shorter hydrolysis times of approximately 30 min [143]. The enzymes most commonly used are b-glucoronidase/ arylsulfatase [144], and pronase [143,145]. For this purpose, proteinase E [146,147] is also used; b-glucoronidase and pronase E were used in a comparative exercise [148]. Baptista et al. [144], employed a b-glucoronidase/arylsulfatase mixture for the extraction of THC, THC-COOH, CBD and CBN. The sample was incubated for 2 h at 40 C, then extracted using an LLE procedure and analysed using GC–MS. The advantages of this technique are the high yield and the ability to directly analyse the solution obtained through an immunochemical method after simple thermal inactivation of the enzyme; an extraction/purification step is required for subsequent chromatographic analysis. The disadvantages of the enzymatic digestion of hair have been considered given the fact that the resulting digest could, under certain conditions, denature the antibodies used for the preliminary detection of drugs by immunoassays [108]. 3.7. Extraction with urea and thioglycolate The extraction of substances from hair in an aqueous medium is facilitated in the presence of denaturants such as urea (8 mol L 1) and thioglycolate (0.2 mol L 1) in acidic conditions (pH 3.2). Exposure to these agents results in breakdown of the hydrogen and disulphide bonds within the hair. This approach has proved particularly effective for the extraction of benzodiazepines [17]. 3.8. Microwave-assisted extraction The MAE technique has been recently used in forensic and clinical analyses. In this technique, the transfer of the analyte particles from the matrix or sample solution to the organic solvent is supported by microwave irradiation, which causes heating of the sample–solvent system according to two mechanisms: ion conduction and dipole rotation in the applied field [64]. MAE presents advantages such as the reduction of extraction time and solvent volume employed; moreover, compared to conventional hydrolysis, simultaneous extractions can be performed in a microwave oven [108]. 4. Cleanup of hair extracts After the extraction or digestion step, which generally represents the most demanding step in terms of analysis time, cleanup of the extract is often required in order to reduce the presence of possible interference caused by organic compounds. This step is particularly important in the case of analyses based on liquid chromatography–mass spectrometry, because of the effects of ion suppression/enhancement, and is generally carried out by LLE [8,9,12,24,27,28,33–36,39,58,59,67,73,74,83,84,90,93,101,102, 104,105,118,120,135,137,138,143,149–154] or by solid phase
22
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
extraction (SPE) [23–26,28,38,42,45,46,48,49,52,61,65,72,75,78, 80,92,97–99,103,111,114,115,126,139,155–158]. Cleanup methods involving solid-phase microextraction (SPME) [86,90,142,159], solid-phase dynamic extraction (SPDE) [85] and supercritical fluid extraction [108] are useful techniques. In addition, SPME allows target preconcentration [86,90,142,159]. Among the SPE methods, those that involve the use of mixedmode cartridges generally produce the cleanest extracts compared to those obtained with the cartridges in the inverse phase; this is explained by the fact that in the first case, one can use stronger washing solvents to remove interference without a significant loss of the analyte during the process. This leads to an increase in the signal-to-noise ratio, allowing the detection of lower amounts of analyte and improved method performance. Cleanup procedures that use mixed-mode cartridges have been proposed for methadone, EDDP [98,128] and multianalyte approaches [61,103]. Recently, HS–SPME has assumed an increasingly important role in the analysis of hair. The analytes are adsorbed directly from the HS of the sample solution (i.e., digested hair) until equilibrium is reached between the three phases (sample, head space and fiber). The fiber can then be positioned in the injector of a GC for the thermal desorption of the analytes [12]. This technique allows the extraction, pre-concentration and cleanup steps to be carried out in a single step, avoiding some of the disadvantages of traditional extraction techniques, such as the need for large volumes of solvent (as in LLE), or the desorption of the analyte in the extraction cartridge in the SPE, which generally involves the use of toxic solvents, and during which clogging of the cartridge can occur. HS–SPME combined with GC–MS has been used for the analysis of hair in the determination of methadone and its metabolites [86,142,159], amphetamines [82,89,134], and benzodiazepines [160]. A further development of the HS–SPME technique is HS solidphase dynamic extraction (HS–SPDE) coupled with GC–MS [42,85]. A hollow needle with an internal coating of polydimethylsiloxane (PDMS) with charcoal is used as a means of extraction and preconcentration. Sampling is performed on the solution headspace by actively (thus, ‘dynamically’) passing the gas through the device using a syringe. The analytes present in the sample are absorbed on the deposited stationary phase. The syringe needle is placed into the injection port of a GC while rapid heating of the needle causes desorption of the analytes. It has been demonstrated that the absolute recovery of an analyte obtained via SPDE is 50% greater than that obtained using the SPME fiber [12]. Although SPME is simple and uses little or no organic solvent, it suffers due to the comparatively expensive and fragile fiber, which has a limited lifetime and results in a sample carry-over effect [22]. Hollow-fiber liquid microextraction (LPME) instead eliminates the carry-over effect since the hollow fibers can be discarded after each extraction due to their low cost [22]; other advantages are simplicity, rapidity, less sample manipulation and low consumption of toxic organic solvents. The major disadvantage is the lack of automation of the process because it is a relatively new technique [22]. Among the new procedures, the use of molecularly imprinted polymers (MIP) has shown interesting results. A method using an MIP as the selective sorbent for solid-phase extraction (SPE) has been developed to evaluate nicotine in tobacco exposure [161]; this MIP–SPE method provided inherent selectivity and a sensitive response to nicotine with a detection limit of 0.2 ng mL 1 hair. Thibert et al. [125] synthesized an MIP using methacrylic acid as a functional monomer, ethylene glycol dimethacrylate as crosslinker and a photochemical initiation for the selective extraction of cocaine and benzoylecgonine. With the MIP, retrievals of almost 80% were obtained for both analytes. Anderson et al. [78] proposed molecularly imprinted solid-phase extraction (MISPE) for the
determination of benzodiazepines in post-mortem hair. The results were compared to those obtained by classic SPE:MISPE demonstrated a higher selectivity with fewer matrix interferences. Finally, matrix solid phase dispersion (MSPD) consists of a sample architecture disruption by mechanical blending with a solid support-bonded phase, which after blending, leads to a new sample matrix solid support phase in which analytes tend to be less strongly bonded. The advantages are reduction of solvent consumption, exclusion of sample component degradation and improvement of extraction efficiency [145]. 5. Discussion Considering Table 1, in which methods that use methanol in the extraction procedure are reported, we can underline that amphetamines are mainly extracted in acidic conditions [25,43, 65,68,70,76,119–124] but also in neutral methanol [26,30,38, 41,63,95,105,107]. The amount of sample used for analysis generally ranges from 10 to 50 mg; the washing step is mainly carried out with dichloromethane in the cases of neutral methanol, while in the case of acidic methanol, a variety of solvent washing procedures have been proposed. As noted in many articles, the extracts generally exhibit a high degree of contamination from the hair matrix, so a further purification step is recommended. This purification step is usually performed by SPE [26,38] or LLE [41,105] but in most of the reported cases for the analysis of amphetamines [30,43,76,119– 124], this step is missing and direct injection in GC–MS is employed after drying and derivatization of the extracts. Benzodiazepines are mainly extracted in neutral [30,37, 71,72,102,107] and basic methanol [17,78,79,100,118]. The sample amount used for the analysis generally ranges from 10 to 100 mg of hair and a variety of washing solvents are employed. The temperature of incubation ranges from 25 C to 55 C and a long incubation time is generally used (16–18 h) [30,37,71,72]. Various cleanup procedures, which use SPE, LLE and filtration, are reported. In most of the reported cases, LC-MS/MS analysis is performed [37,71,78,79,102,117]. An aliquot of 10–50 mg of hair is extracted using methanol when cocaine and opiates are considered. Dichloromethane is the most common washing solvent while SPE is the cleanup procedure most often employed [25,26,28,38,111,112]. Both GC–MS [26,28,38,112] and LC-MS/MS [111] analyses are conducted. When considering the two studies reported in Table 2, in which the extraction of all the drugs is performed with acetonitrile, 50 mg of hair are washed with dichloromethane in both cases. In the first study [27], an LLE followed by an SPE is performed before LC-MS/ MS analysis; in the second case [125], an MIP is synthesized and evaluated before LC–MS analysis. Target drugs can also be extracted by aqueous or buffer solutions, as previously reported in Table 3. Amphetamines (aliquots of 10–200 mg of hair) are mainly extracted with HCl 0.1 or 1 M before an LLE [67,104] or SPE [49,91,94,103]. The analytical technique may vary from GC–MS [49,91,94,103,104] to LC-MS/MS [60,80,127]. For the determination of cocaine [45,48,52,91,94,97,99,103,126], opiates [45,49,52,103] and methadone [91,94,128], a similar extraction procedure used for amphetamines is employed, but the cleanup is conducted by SPE followed by a GC–MS analysis in most of the reported cases. Conversely, the extraction procedure for benzodiazepines uses, in most cases, 20 mg of hair sample incubated in a buffer phosphate solution pH 8.4, prior to an LLE cleanup and LC-MS/ MS analysis [8,33,36,62,106]. It is worth mentioning Table 4, which describes methods employing solvent mixtures for hair extraction: in these works
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
[19,50,66,75,77,81,93,108,109,130–132], high resolution techniques, together with an effective extraction procedure, allow the utilization of a small amount of hair sample. Specifically, in almost all the reported studies, drugs of interest are determined using 0.2–20 mg of sample. In particular, in the same studies, a new approach to sample preparation consisting of micropulverization and simultaneous extraction were proposed in order to increase the speed and simplicity of hair analysis [19,66,77,109,131]. All these approaches allow the direct injection of hair extracts into the LC–HRMS, LC-MS/MS or UPLC–MS instruments. Table 5 reports the methods proposed in the literature that involve extraction with NaOH; this approach has been demonstrated to be particularly advantageous for the extraction of amphetamines and cannabinoids. Generally, the sample amount used ranges from 10 to 50 mg and the extraction procedure, consisting of incubation with 1–2 mL NaOH (1–10 M) for 10–60 min at temperatures of 70–100 C, is similar in all the reported cases. While for cannabinoids, an LLE procedure is preferred for sample cleanup [34,35,51,53–58,84,138,141], in the case of amphetamines, LLE and SPE are indifferently used. In almost all these works, analysis is performed by GC–MS, after a derivatization step [39,69,82,96,134,135]. To summarize, a direct comparison of the extraction and purification methods to determine the most effective approach for a specific class of drugs is not possible because the LODs and LOQs are indicative of the entire method and are also affected by the conditions of both the chromatograph and mass spectrometer used. 6. Conclusions Utilization of hair as a tool for identifying the use of substances of abuse is becoming increasingly applicable in clinical and forensic toxicology. Among the various phases comprising the analysis of hair, the stages of decontamination, extraction and purification (cleanup) of the sample have been reviewed in this work. Although it is mandatory to include a decontamination step, there is no consensus on which procedure performs best and a variety of combinations of solvents (either protic, hydrophilic or hydrophobic) have been proposed for each class of substances. As for the extraction step, a universal procedure able to ensure optimum yields for all classes of substances does not exist; in order to make an appropriate extraction procedure choice, the chemical structure of the analyte to be extracted and its sensitivity to agents used in the preparation of the sample must be considered. Particularly attention must be devoted to analytes that can undergo hydrolysis (heroin, 6-MAM, cocaine, benzoylecgonine). Simple methanol extraction is certainly the one proposed in the greatest number of cases because it is a method with a broad spectrum of use, compatible with almost all substances of abuse and it does not entail the undesirable phenomenon of analyte hydrolysis. The methanolic extracts exhibit a high degree of contamination by hair and very specific LC–MS methods of detection are required, such as multi-reaction monitoring (MRM) or HRMS, to directly analyse the extracts after filtration. Cleaner extracts were obtained using an alternative solvent, acetonitrile. The few cases existing in the literature that involve its use seem to indicate its suitability for the extraction of a wide range of analytes with good extraction yields. The basic substances are extracted effectively in neutral or slightly acid environments. The main advantage of this type of extraction is the ability to simultaneously analyse opiates, cocaine, amphetamines, methadone and pharmaceutical drugs (i.e., benzodiazepines).
23
For substances that are stable in alkaline conditions, an effective method of extraction from hair samples consists of digestion with an aqueous solution of NaOH that completely dissolves the hair matrix. Such extraction is particularly advantageous for amphetamines, but is less suitable for other classes since in these conditions, the hydrolysis of heroin, monoacetylmorphine and cocaine can occur. The most current request in the analysis of hair consists of the development of multianalyte methods that allow rapid screening for different classes of substances, preferably to be performed ina single procedure and on small quantities of sample. This perspective includes the tendency to use, in some recently proposed methods, mixtures of solvents of extraction, which often constitute the mobile phase of the subsequent LC–MS analysis. These approaches allow the direct injection of the extracts obtained, avoiding long and expensive purification steps. When required by the analytical method (i.e., GC–MS or GC-MS/ MS), the cleanup procedure consists mostly of an LLE or an SPE. Among SPE techniques, there are those that include the use of mixed-mode cartridges capable of producing extracts cleaner than classic SPE; HS–SPME techniques, in which pre-concentration of the sample and cleanup occurs in a single step; HS–SPDE techniques, which represent an evolution of HS–SPME, and can provide complete retrievals of analyte greater than 50% compared to those obtained with SPME fiber; the use of supercritical fluids in SFE, a miniaturized and automated technique that is somewhat expensive, but able to produce a high extraction yield; and techniques that involve the use of MIP, tested for the selective extraction of cocaine and benzoylecgonine or benzodiazepines, which have provided larger extraction yields compared to the other techniques. The trend towards simplification of sample preparation and a reduction in the amount of sample used has been made possible by recent advances in the sensitivity of the analytical techniques employed (GC–HRMS, LC–MSn, LC–HRMS, LC–chip–MSn). This has led to increases in specificity and sensitivity, favoring the use of lower amounts of sample and purification steps, with a progressive reduction in LOD and LOQ values. Using a sample amount of less than 10 mg, the lowest LOQ values for amphetamine and cocaine analysis were obtained by Zhu et al. [77] using a nano-HPLC-chip-MS/MS technique, by Myhaguchi et al. [66] using LC–MS–MS, and by Favretto et al. [19] with LC–HRMS. Zhu et al. [77] and Favretto et al. [19] also obtained the lowest LOQs for the determination of methadone and opiates by using, respectively, 2 and 2.5 mg of hair. References [1] M. Barroso, E. Gallardo, D.N. Vieira, J.A. Queiroz, M. López-Rivadulla, Bioanalytical procedures and recent developments in the determination of opiates/opioids in human biological samples, Anal. Bioanal. Chem. 400 (2011) 1665–1690. [2] K. Saito, R. Saito, Y. Kikuchi, Y. Iwasaki, R. Ito, H. Nakazawa, Analysis of drugs of abuse in biological specimens, J. Health Sci. 57 (6) (2011) 472–487. [3] M. Vincenti, A. Salomone, E. Gerace, V. Pirro, Role of LC-MS/MS in hair testing for the determination of common drugs of abuse and other psychoactive drugs, Bioanalysis 5 (15) (2013) 1919–1938. [4] I.M. Kempson, E. Lombi, Hair analysis as a biomonitor for toxicology, disease and health status, Chem. Soc. Rev. 40 (2011) 3915–3940. [5] P. Kintz, M. Villain, V. Crimele, Hair analysis for drug detection, Ther. Drug Monit. 28 (3) (2006) 442–446. [6] G. Frison, D. Favretto, L. Tedeschi, S.D. Ferrara, Detection of thiopental and pentobarbital in head and pubic hair in a case of drug facilitated sexual assault, Forensic Sci. Int. 133 (1–2) (2003) 171–174. [7] M. Fisichella, L. Morini, C. Sempio, A. Groppi, Validation of a multi-analyte LCMS/MS method for screening and quantification of 87 psychoactive drugs and their metabolites in hair, Anal. Bioanal. Chem. (2014) , doi:http://dx.doi.org/ 10.1007/S00216-014-7763-2. [8] P. Kintz, M. Villain, V. Cirimele, G. Pépin, B. Ludes, Windows of detection of lorazepam in urine, oral fluid and hair, with a special focus on drug-facilitated crimes, Forensic Sci. Int. 145 (2–3) (2004) 131–135.
24
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
[9] P. Kintz, M. Villain, M. Chèze, G. Pépin, Identification of alprazolam in hair in two cases of drug-facilitated incidents, Forensic Sci. Int. 153 (2–3) (2005) 222–226. [10] M. Villain, M. Chèze, V. Dumestre, B. Ludes, P. Kintz, Hair to document drugfacilitated crimes: four cases involving bromazepam, J. Anal. Toxicol. 28 (6) (2004) 516–519. [11] D. Favretto, G. Stocchero, A. Nalesso, S. Vogliardi, R. Boscolo-Berto, M. Montisci, S.D. Ferrara, Monitoring haloperidol exposure in body fluids and hair of children by liquid chromatography-high-resolution mass spectrometry, Ther. Drug Monit. 35 (4) (2013) 493–501. [12] F. Musshoff, B. Madea, New trends in hair analysis and scientific demands on validation and technical notes, Forensic Sci. Int. 165 (2007) 204–215. [13] G.L. Henderson, Mechanism of drug incorporation into hair, Forensic Sci. Int. 63 (1993) 19–29. [14] P.E. Van Erp, M.J. Jansen, G.J. De Jongh, J.B. Boezeman, J. Shalkwijk, Radiometric measurement of intracellular pH in cultured human keratinocytes using carboxy-SNARF-1 and flow cytometry, Cytometry 12 (1991) 127– 132. [15] L. Pötsch, G. Skopp, G. Rippin, A comparison of H-cocaine binding on melanin granules and human hair in vitro, Int. J. Leg. Med. 110 (1997) 55–62. [16] D.J. Claffey, P.R. Stout, J.A. Ruth, 3H-nicotine, 3H-flunitrazepam, 3H-cocaine incorporation into melanin: a model for the examination of drug–melanin interactions, J. Anal. Toxicol. 25 (2001) 607–611. [17] M. Yegles, Y. Marson, R. Wennig, Influence of bleaching on stability of benzodiazepines in hair, Forensic Sci. Int. 107 (2000) 87–92. [18] M. Vincenti, A. Salomone, E. Gerace, V. Pirro, Application of mass spectrometry to hair analysis for forensic toxicological investigations, Mass Spec. Rev. 32 (2013) 312–332. [19] D. Favretto, S. Vogliardi, G. Stocchero, A. Nalesso, M. Tucci, S.D. Ferrara, High performance liquid chromatography–high resolution mass spectrometry and micropulverized extraction for the quantification of amphetamines, cocaine, opioids, benzodiazepines, antidepressants and hallucinogens in 2.5 mg hair samples, J. Chromatogr. A 1218 (38) (2011) 6583–6595. [20] F. Pragst, M.A. Balikova, State of the art in hair analysis for detection of drug and alcohol abuse, Clin. Chim. Acta. 370 (2006) 17–49. [21] M.I. Schaffer, W.L. Wang, J. Irving, An evaluation of two wash procedures for the differentiation of external contamination versus ingestion in the analysis of human hair samples for cocaine, J. Anal. Toxicol. 26 (2002) 485–488. [22] L. Pantaleão, B.A.P.B. Paranhos, M. Yonamine, Hallow-fiber liquid-phase microextraction of amphetamine-type stimulants in human hair samples, J. Chromatogr. A 1254 (2012) 1–7. [23] C.A. Moore, F. Guzaldo, T. Donahue, The determination of 11-nor-delta9tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in hair using negative ion gas chromatography–mass spectrometry and high-volume injection, J. Anal. Toxicol. 25 (2001) 555–558. [24] C. Moore, S. Rana, C. Coulter, F. Feyerherm, H. Prest, Application of twodimensional gas chromatography with electron capture chemical ionization mass spectrometry to the detection of 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in hair, J. Anal. Toxicol. 30 (3) (2006) 171–177. [25] Y.H. Wu, K.L. Lin, S.C. Chen, Y.Z. Chang, Integration of GC/EI-MS and GC/NCIMS for simultaneous quantitative determination of opiates, amphetamines, MDMA, ketamine, and metabolites in human hair, J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 870 (2) (2008) 192–202. [26] Y.H. Wu, K.L. Lin, S.C. Chen, Y.Z. Chang, Simultaneous quantitative determination of amphetamines, ketamine, opiates and metabolites in human hair by gas chromatography/mass spectrometry, Rapid Commun. Mass Spectrom. 22 (6) (2008) 887–897. [27] E. Lendoiro, O. Quintela, A. de Castro, A. Cruz, M. López-Rivadulla, M. Concheiro, Target screening and confirmation of 35 licit and illicit drugs and metabolites in hair by LC–MS–MS, Forensic Sci. Int. 217 (1–3) (2012) 207– 215. [28] L. Skender, V. Karaci c, I. Brci c, A. Bagari c, Quantitative determination of amphetamines, cocaine, and opiates in human hair by gas chromatography/ mass spectrometry, Forensic Sci. Int. 125 (2–3) (2002) 120–126. [29] J.P. Selten, I.J. Bosman, D. de Boer, N.D. Veen, Y. van der Graaf, R.A. Maes, R.S. Kahn, Hair analysis for cannabinoids and amphetamines in a psychosis incidence study, Eur. Neuropsychopharmacol. 12 (1) (2002) 27–30. [30] S. Paterson, N. McLachlan-Troup, R. Cordero, M. Dohnal, S. Carman, Qualitative screening for drugs of abuse in hair using GC–MS, J. Anal. Toxicol. 25 (3) (2001) 203–208. [31] S. Paterson, R. Cordero, M. McPhillips, S. Carman, Interindividual dose/ concentration relationship for methadone in hair, J. Anal. Toxicol. 27 (1) (2003) 20–23. [32] M. Chèze, M. Villain, G. Pépin, Determination of bromazepam, clonazepam and metabolites after a single intake in urine and hair by LC-MS/MS. Application to forensic cases of drug facilitated crimes, Forensic Sci. Int. 145 (2–3) (2004) 123–130. [33] M. Villain, M. Concheiro, V. Cirimele, P. Kintz, Screening method for benzodiazepines and hypnotics in hair at pg/mg level by liquid chromatography-mass spectrometry/mass spectrometry, J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 825 (1) (2005) 72–78. [34] R. Marsili, S. Martello, M. Felli, S. Fiorina, M. Chiaretti, Hair testing for D9THC-COOH by gas chromatography/tandem mass spectrometry in negative chemical ionization mode, Rapid Comm. Mass Spectrom. 19 (2005) 1566– 1568.
[35] G. Skopp, P. Strohbeck-Kuehner, K. Mann, D. Hermann, Deposition of cannabinoids in hair after long-term use of cannabis, Forensic Sci. Int. 170 (1) (2007) 46–50. [36] P. Xiang, Q. Sun, B. Shen, P. Chen, W. Liu, M. Shen, Segmental hair analysis using liquid chromatography-tandem mass spectrometry after a single dose of benzodiazepines, Forensic Sci. Int. 204 (1–3) (2011) 19–26. [37] A. Salomone, E. Gerace, D. Di Corcia, G. Martra, M. Petrarulo, M. Vincenti, Hair analysis of drugs involved in drug-facilitated sexual assault and detection of zolpidem in a suspected case, Int. J. Legal Med. 126 (3) (2012) 451–459. [38] K. Aleksa, P. Walasek, N. Fulga, B. Kapur, J. Gareri, G. Koren, Simultaneous detection of seventeen drugs of abuse and metabolites in hair using solid phase micro extraction (SPME) with GC/MS, Forensic Sci. Int. 218 (1–3) (2012) 31–36. [39] M. Pujadas, S. Pichini, S. Poudevida, E. Menoyo, P. Zuccaro, M. Farré, R. de la Torre, Development and validation of a gas chromatography-mass spectrometry assay for hair analysis of amphetamine, methamphetamine and methylenedioxy derivatives, J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 798 (2) (2003) 249–255. [40] S. Cristoni, E. Basso, P. Gerthoux, P. Mocarelli, E. Gonella, M. Brambilla, S. Crotti, L.R. Bernardi, Surface-activated chemical ionization ion trap mass spectrometry for the analysis of cocaine and benzoylecgonine in hair after extraction and sample dilution, Rapid Commun. Mass Spectrom. 21 (15) (2007) 2515–2523. [41] M.L. Pujol, V. Cirimele, P.J. Tritsch, M. Villain, P. Kintz, Evaluation of the IDS One-Step ELISA kits for the detection of illicit drugs in hair, Forensic Sci. Int. 170 (2–3) (2007) 189–192. [42] K. Lachenmeier, F. Musshoff, B. Madea, Determination of opiates and cocaine in hair using automated enzyme immunoassay screening methodologies followed by gas chromatographic–mass spectrometric (GC–MS) confirmation, Forensic Sci. Int. 159 (2006) 189–199. [43] S. Lee, E. Han, Y. Park, H. Choi, H. Chung, Distribution of methamphetamine and amphetamine in drug abusers’ head hair, Forensic Sci. Int. 190 (1–3) (2009) 16–18. [44] C. Moore, F. Guzaldo, T. Donahue, The determination of 11-nor-delta9tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in hair using negative ion gas chromatography–mass spectrometry and high-volume injection, J. Anal. Toxicol. 25 (7) (2001) 555. [45] M. Montagna, C. Stramesi, C. Vignali, A. Groppi, A. Polettini, Simultaneous hair testing for opiates, cocaine, and metabolites by GC–MS: a survey of applicants for driving licenses with a history of drug use, Forensic Sci. Int. 107 (1–3) (2000) 157–167. [46] F.S. Romolo, M.C. Rotolo, I. Palmi, R. Pacifici, A. Lopez, Optimized conditions for simultaneous determination of opiates, cocaine and benzoylecgonine in hair samples by GC–MS, Forensic Sci. Int. 138 (2003) 17–26. [47] M. Felli, S. Martello, R. Marsili, M. Chiarotti, Disappearance of cocaine from human hair after abstinence, Forensic Sci. Int. 154 (2005) 96–98. [48] L. Mercolini, R. Mandrioli, B. Saladini, M. Conti, C. Baccini, M.A. Raggi, Quantitative analysis of cocaine in human hair by HPLC with fluorescence detection, J. Pharm. Biomed. Anal. 48 (2) (2008) 456–461. [49] B. Guthery, T. Bassindale, A. Bassindale, C.T. Pillinger, G.H. Morgan, Qualitative drug analysis of hair extracts by comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry, J. Chromatogr. A 1217 (26) (2010) 4402–4410. [50] M.K. Nielsen, S.S. Johansen, P.W. Dalsgaard, K. Linnet, Simultaneous screening and quantification of 52 common pharmaceuticals and drugs of abuse in hair using UPLC–TOF–MS, Forensic Sci. Int. 196 (1–3) (2010) 85–92. [51] E.A. Han, H. Choi, S. Lee, H. Chung, J.M. Song, A study on the concentrations of 11-nor-(9)-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in hair root and whole hair, Forensic Sci. Int. 210 (2011) 201–205. [52] M. Montagna, A. Polettini, C. Stramesi, A. Groppi, C. Vignali, Hair analysis for opiates, cocaine and metabolites: evaluation of a method by interlaboratory comparison, Forensic Sci. Int. 128 (2002) 79–83. [53] E. Han, W. Yang, S. Lee, E. Kim, S. In, H. Choi, S. Lee, H. Chung, J.M. Song, Establishment of the measurement uncertainty of 11-nor-D9-tetrahydrocannabinol-9-carboxylic acid in hair, Forensic Sci. Int. 206 (1–3) (2011) e85–e92. [54] E. Han, Y. Park, E. Kim, S. In, W. Yang, S. Lee, H. Choi, S. Lee, H. Chung, J.M. Song, Simultaneous analysis of (9)-tetrahydrocannabinol and 11-nor-9-carboxytetrahydrocannabinol in hair without different sample preparation and derivatization by gas chromatography-tandem mass spectrometry, J. Pharm. Biomed. Anal. 55 (5) (2011) 1096–1103. [55] E. Han, H. Choi, S. Lee, H. Chung, J.M. Song, A comparative study on the concentrations of 11-nor-(9-tetrahydrocannabinol-9-carboxylic acid (THCCOOH) in head and pubic hair, Forensic Sci. Int. 212 (1–3) (2011) 238–241. [56] J.Y. Kim, S.I. Suh, M.K. In, K.J. Paeng, B.C. Chung, Simultaneous determination of cannabidiol, cannabinol, and delta9-tetrahydrocannabinol in human hair by gas chromatography–mass spectrometry, Arch. Pharm. Res. 28 (9) (2005) 1086–1091. [57] J.Y. Kim, J.C. Cheong, J.I. Lee, M.K. In, Improved gas chromatography-negative ion chemical ionization tandem mass spectrometric method for determination of 11-nor-(9-tetrahydrocannabinol-9-carboxylic acid in hair using mechanical pulverization and bead-assisted liquid–liquid extraction, Forensic Sci. Int. 206 (1–3) (2011) e99–e102. [58] J.Y. Kim, Moon Kyo In, Determination of 11-nor-D9-tetrahydrocannabinol-9carboxylic acid in hair using gas chromatography/tandem mass spectrometry in negative ion chemical ionization mode, Rapid Commun. Mass Spectrom. 21 (2007) 1339–1342.
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27 [59] P. Meng, N. Fang, M. Wang, H. Liu, D.D. Chen, Analysis of amphetamine, methamphetamine and methylenedioxy-methamphetamine by micellar capillary electrophoresis using cation-selective exhaustive injection, Electrophoresis 27 (16) (2006) 3210–3217. [60] F. Tagliaro, R. Valentini, G. Manetto, F. Crivellente, G. Carli, M. Marigo, Hair analysis by using radioimmunoassay, high-performance liquid chromatography and capillary electrophoresis to investigate chronic exposure to heroin, cocaine and/or ecstasy in applicants for driving licences, Forensic Sci. Int. 107 (1–3) (2000) 121–128. [61] A. Pelander, J. Ristimaa, I. Rasanen, E. Vuori, I. Ojanperä, Screening for basic drugs in hair of drug addicts by liquid chromatography/time-of-flight mass spectrometry, Ther. Drug Monit. 30 (6) (2008) 717–724. [62] S. Vogliardi, D. Favretto, M. Tucci, G. Stocchero, S.D. Ferrara, Simultaneous LC– HRMS determination of 28 benzodiazepines and metabolites in hair, Anal. Bioanal. Chem. 400 (1) (2011) 51–67. [63] M. Kłys, S. Rojek, J. Kulikowska, E. Bozek, M. Scisłowski, Usefulness of multiparameter opiates-amphetamines-cocainics analysis in hair of drug users for the evaluation of an abuse profile by means of LC–APCI–MS–MS, J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 854 (1–2) (2007) 299–307. [64] R. Wietecha-Posluszny, M. Wozniakiewicz, A. Garbacik, P. Chesy, P. Koscielniak, Application of microwave irradiation to fast and efficient isolation of benzodiazepines from human hair, J. Chromatogr. A 1278 (2013) 22–28. [65] A.B. Miki, M. Katagi, H. Tsuchihashi, Determination of methamphetamine and its metabolites incorporated in hair by column-switching liquid chromatography–mass spectrometry, J. Anal. Toxicol. 27 (2) (2003) 95–102. [66] H. Miyaguchi, H. Inoue, Determination of amphetamine-type stimulants, cocaine and ketamine in human hair by liquid chromatography/linear ion trap-Orbitrap hybrid mass spectrometry, Analyst 136 (17) (2011) 3503–3511. [67] Y.H. Lin, M.R. Lee, R.J. Lee, W.K. Ko, S.M. Wu, Hair analysis for methamphetamine, ketamine, morphine and codeine by cation-selective exhaustive injection and sweeping micellar electrokinetic chromatography, J. Chromatogr. A 1145 (1–2) (2007) 234–240. [68] K. Nakashima, A. Kaddoumi, Y. Ishida, T. Itoh, K. Taki, Determination of methamphetamine and amphetamine in abusers’ plasma and hair samples with HPLC-FL, Biomed. Chromatogr. 17 (7) (2003) 471–476. [69] M. Nishida, M. Yashiki, A. Namera, K. Kimura, Single hair analysis of methamphetamine and amphetamine by solid phase microextraction coupled with in matrix derivatization, J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 842 (2) (2006) 106–110. [70] O.Y. Al-Dirbashi, N. Kuroda, M. Wada, M. Takahashi, K. Nakashima, Quantification of methamphetamine, amphetamine and enantiomers by semi-micro column HPLC with fluorescence detection; applications on abusers’ single hair analyses, Biomed. Chromatogr. 14 (5) (2000) 293–300. [71] J. Kim, S. Lee, S. In, H. Choi, H. Chung, Validation of a simultaneous analytical method for the detection of 27 benzodiazepines and metabolites and zolpidem in hair using LC-MS/MS and its application to human and rat hair, J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 879 (13–14) (2011) 878–886. [72] S. Lee, E. Han, S. In, H. Choi, H. Chung, K.H. Chung, Determination of illegally abused sedative-hypnotics in hair samples from drug offenders, J. Anal. Toxicol. 35 (5) (2011) 312–315. [73] R.C. Irving, S.J. Dickson, The detection of sedatives in hair and nail samples using tandem LC–MS–MS, Forensic Sci. Int. 166 (1) (2007) 58–67. [74] S.S. Johansen, J. Jornil, Determination of amphetamine, methamphetamine, MDA and MDMA in human hair by GC–EI–MS after derivatization with perfluorooctanoyl chloride, Scand. J. Clin. Lab Invest. 69 (1) (2009) 113–120. [75] S. Hegstad, H.Z. Khiabani, L. Kristoffersen, N. Kunøe, P.P. Lobmaier, A.S. Christophersen, Drug screening of hair by liquid chromatography-tandem mass spectrometry, J. Anal. Toxicol. 32 (5) (2008) 364–372. [76] G. Frison, L. Tedeschi, D. Favretto, A. Reheman, S.D. Ferrara, Gas chromatography/mass spectrometry determination of amphetamine-related drugs and ephedrines in plasma, urine and hair samples after derivatization with 2,2,2trichloroethyl chloroformate, Rapid Commun. Mass Spectrom. 19 (7) (2005) 919–927. [77] K.Y. Zhu, K.W. Leung, A.K.L. Ting, Z.C.F. Wong, W.Y.Y. Ng, R.C.Y. Choi, T.T.X. Dong, T. Wang, D.T.W. Lau, K.W.K. Tsim, Microfluidic chip based nano liquid chromatography coupled to tandem mass spectrometry for the determination of abused drugs and metabolites in human hair, Anal. Bioanal. Chem. 402 (2012) 2805–2815. [78] R.A. Anderson, M.M. Ariffin, P.A. Cormack, E.I. Miller, Comparison of molecularly imprinted solid-phase extraction (MISPE) with classical solidphase extraction (SPE) for the detection of benzodiazepines in post-mortem hair samples, Forensic Sci. Int. 174 (1) (2008) 40–46. [79] E.I. Miller, F.M. Wylie, J.S. Oliver, Detection of benzodiazepines in hair using ELISA and LC–ESI–MS–MS, J. Anal. Toxicol. 30 (7) (2006) 441–448. [80] E.I. Miller, F.M. Wylie, J.S. Oliver, Simultaneous detection and quantification of amphetamines, diazepam and its metabolites, cocaine and its metabolites, and opiates in hair by LC–ESI–MS–MS using a single extraction method, J. Anal. Toxicol. 32 (7) (2008) 457–469. [81] M. Sergi, S. Napoletano, C. Montesano, R. Iofrida, R. Curini, D. Campagnone, Pressurized-liquid extraction for determination of illicit drugs in hair by LC– MS–MS, Anal. Bioanal. Chem. 405 (2013) 725–735. [82] F. Musshoff, H.P. Junker, D.W. Lachenmeier, L. Kroener, B. Madea, Fully automated determination of amphetamines and synthetic designer drugs in hair samples using headspace solid-phase microextraction and gas
[83]
[84]
[85]
[86]
[87]
[88]
[89]
[90]
[91]
[92]
[93]
[94]
[95]
[96]
[97]
[98]
[99]
[100]
[101]
[102]
[103]
[104]
25
chromatography–mass spectrometry, J. Chromatogr. Sci. 40 (6) (2002) 359–364. M. Chèze, M. Deveaux, C. Martin, M. Lhermitte, G. Pépin, Simultaneous analysis of six amphetamines and analogues in hair, blood and urine by LCESI-MS/MS. Application to the determination of MDMA after low ecstasy intake, Forensic Sci. Int. 170 (2–3) (2007) 100–104. V. Auwärter, A. Wohlfarth, J. Traber, D. Thieme, W. Weinmann, Hair analysis for Delta9-tetrahydrocannabinolic acid A-new insights into the mechanism of drug incorporation of cannabinoids into hair, Forensic Sci. Int. 196 (1–3) (2010) 10–13. F. Musshoff, D.W. Lachenmeier, L. Kroener, B. Madea, Automated headspace solid-phase dynamic extraction for the determination of cannabinoids in hair samples, Forensic Sci. Int. 133 (2003) 32–38. F. Musshoff, H.P. Junker, D.W. Lachenmeier, L. Kroener, B. Madea, Fully automated determination of cannabinoids in hair samples using headspace solid-phase microextraction and gas chromatography–mass spectrometry, J. Anal. Toxicol. 26 (2002) 554–560. E.S. Emídio, V. de Menezes Prata, F.J. de Santana, H.S. Dórea, Hollow fiberbased liquid phase microextraction with factorial design optimization and gas chromatography-tandem mass spectrometry for determination of cannabinoids in human hair, J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 878 (24) (2010) 2175–2183. E.S. Emídio, M. Prata Vde, H.S. Dórea, Validation of an analytical method for analysis of cannabinoids in hair by head space solid-phase microextraction and gas chromatography-ion trap tandem mass spectrometry, Anal. Chim. Acta 670 (1–2) (2010) 63–71. S. Gentili, A. Torresi, R. Marsili, M. Chiarotti, T. Macchia, Simultaneous detection of amphetamine-like drugs with headspace solid-phase microextraction and gas chromatography–mass spectrometry, J. Chromatogr. B 780 (2002) 183–192. T. Nadulski, F. Pragst, Simple and sensitive determination of Delta (9)tetrahydrocannabinol, cannabidiol and cannabinol in hair by combined silylation, headspace solid phase microextraction and gas chromatography– mass spectrometry, J. Chromatogr. B 846 (2007) 78–85. S.A. Gentili, M. Cornetta, T. Macchia, Rapid screening procedure based on headspace solid-phase microextraction and gas chromatography–mass spectrometry for the detection of many recreational drugs in hair, J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 801 (2) (2004) 289–296. L.F. Martins, M. Yegles, N. Samyn, J.G. Ramaekers, R. Wennig, Time-resolved hair analysis of MDMA enantiomers by GC/MS-NCI, Forensic Sci. Int. 172 (2–3) (2007) 150–155. S. Broecker, S. Herre, F. Pragst, General unknown screening in hair by liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC– QTOF–MS), Forensic Sci. Int. 218 (1–3) (2012) 68–81. G. Merola, S. Gentili, F. Tagliaro, T. Macchia, Determination of different recreational drugs in hair by HS–SPME and GC/MS, Anal. Bioanal. Chem. 397 (7) (2010) 2987–2995. J.Y. Kim, S.H. Shin, J.I. Lee, M.K. In, Rapid and simple determination of psychotropic phenylalkylamine derivatives in human hair by gas chromatography–mass spectrometry using micro-pulverized extraction, Forensic Sci. Int. 196 (1–3) (2010) 43–50. L. Martins, M. Yegles, H. Chung, R. Wennig, Simultaneous enantioselective determination of amphetamine and congeners in hair specimens by negative chemical ionization gas chromatography–mass spectrometry, J. Chromatogr. B 825 (2005) 57–62. E. Cognard, S. Rudaz, S. Bouchonnet, C. Staub, Analysis of cocaine and three of its metabolites in hair by gas chromatography–mass spectrometry using iontrap detection for CI/MS/MS, J. Chromatogr. B 826 (2005) 17–25. M. Barroso, M. Dias, D.N. Vieira, M. López-Rivadulla, J.A. Queiroz, Mixedmode solid-phase extraction for sample cleanup in hair analysis for methadone and its main metabolite, Biomed. Chromatogr. 24 (11) (2010) 1240–1246. M. Barroso, M. Dias, D.N. Vieira, J.A. Queiroz, M. López-Rivadulla, Development and validation of an analytical method for the simultaneous determination of cocaine and its main metabolite, benzoylecgonine, in human hair by gas chromatography/mass spectrometry, Rapid Commun. Mass Spectrom. 22 (20) (2008) 3320–3326. A. El Mahjoub, C. Staub, Determination of benzodiazepines in human hair by on-line high-performance liquid chromatography using a restricted access extraction column, Forensic Sci. Int. 123 (1) (2001) 17–25. R. Stanaszek, W. Piekoszewski, Simultaneous determination of eight underivatized amphetamines in hair by high-performance liquid chromatographyatmospheric pressure chemical ionization mass spectrometry (HPLC–APCI– MS), J. Anal. Toxicol. 28 (2) (2004) 77–85. M. Laloup, M. Ramirez Fernandez Mdel, G. De Boeck, M. Wood, V. Maes, N. Samyn, Validation of a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of 26 benzodiazepines and metabolites, zolpidem and zopiclone, in blood, urine, and hair, J. Anal. Toxicol. 29 (7) (2005) 616–626. R. Cordero, S. Paterson, Simultaneous quantification of opiates, amphetamines, cocaine and metabolites and diazepam and metabolite in a single hair sample using GC–MS, J. Chromatogr. B 850 (2007) 423–431. K. Beránková, V. Habrdová, M. Balíková, P. Strejc, Methamphetamine in hair and interpretation of forensic findings in a fatal case, Forensic Sci. Int. 153 (1) (2005) 93–97.
26
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27
[105] Z. Es’haghi, M. Mohtaji, M. Hasanzade-Meidani, M. Masrournia, The measurement of ecstasy in human hair by triple phase directly suspended droplet microextraction prior to HPLC-DAD analysis, J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 878 (11–12) (2010) 903–908. [106] L. Morini, C. Vignali, M. Polla, A. Sponta, A. Groppi, Comparison of extraction procedures for benzodiazepines determination in hair by LC-MS/MS, Forensic Sci. Int. 218 (1–3) (2012) 53–56. [107] J.C. Domínguez-Romero, J.F. García-Reyes, A. Molina-Díaz, Screening and quantitation of multiclass drugs of abuse and pharmaceuticals in hair by fast liquid chromatography electrospray time-of-flight mass spectrometry, J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 879 (22) (2011) 2034– 2042. [108] P. Fernandez, M. Lago, R.A. Lorenzo, A.M. Carro, A.M. Bermejo, M.J. Tabernero, Optimization of a rapid microwave-assisted extraction method for the simultaneous determination of opiates, cocaine and their metabolites in human hair, J. Chromatogr. B 877 (2009) 1743–1750. [109] H. Miyaguchi, M. Kakuta, Y.T. Iwata, H. Matsuda, H. Tazawa, H. Kimura, H. Inoue, Development of a micropulverized extraction method for rapid toxicological analysis of methamphetamine in hair, J. Chromatogr. A 1163 (1– 2) (2007) 43–48. [110] F. Garcia-Bournissen, B. Rokach, T. Karaskov, G. Koren, Cocaine detection in maternal and neonatal hair: implications to fetal toxicology, Ther. Drug Monit. 29 (1) (2007) 71–76. [111] K.B. Scheidweiler, M.A. Huestis, Simultaneous quantification of opiates, cocaine, and metabolites in hair by LC-APCI-MS/MS, Anal. Chem. 76 (2004) 4358–4363. [112] F.C.P. De Toledo, M. Yonamine, R.L. De Moraes Moreau, O.A. Silva, Determination of cocaine, benzoylecgonine and cocaethylene in human hair by solid-phase microextraction and gas chromatography–mass spectrometry, J. Chromatogr. B 798 (2003) 361–365. [113] D.K. Huang, C. Liu, M.K. Huang, C.S. Chien, Simultaneous determination of morphine, codeine, 6-acetylmorphine, cocaine and benzoylecgonine in hair by liquid chromatography/electrospray ionization tandem mass spectrometry, Rapid Commun. Mass Spectrom. 23 (2009) 957–962. [114] G. Cooper, L. Wilson, C. Reid, D. Baldwin, C. Hand, V. Spiehler, Comparison of Cozart microplate ELISA and GC–MS detection of methadone and metabolites in human hair, J. Anal. Toxicol. 29 (7) (2005) 678–681. [115] M. Uhl, H. Sachs, Cannabinoids in hair: strategy to prove marijuana/hashish consumption, Forensic Sci. Int. 145 (2004) 143–147. [116] U. Backofen, W. Hoffmann, F.M. Matysik, Determination of cannabinoids by capillary liquid chromatography with electrochemical detection, Biomed. Chromatogr. 14 (1) (2000) 49. [117] K.Y. Rust, M.R. Baumgartner, N. Meggiolaro, T. Kraemer, Detection and validated quantification of 21 benzodiazepines and 3 z-drugs in human hair by LC-MS/MS, Forensic Sci. Int. 215 (1–3) (2012) 64–72. [118] O. García-Algar, M.A. López-Vílchez, I. Martín, A. Mur, M. Pellegrini, R. Pacifici, S. Rossi, S. Pichini, Confirmation of gestational exposure to alprazolam by analysis of biological matrices in a newborn with neonatal sepsis, Clin. Toxicol. (Phila.) 45 (3) (2007) 295–298. [119] E. Han, W. Yang, J. Lee, Y. Park, E. Kim, M. Lim, H. Chung, Correlation of methamphetamine results and concentrations between head, axillary, and pubic hair, Forensic Sci. Int. 147 (1) (2005) 21–24. [120] S. Baeck, E. Han, H. Chung, M. Pyo, Effects of repeated hair washing and a single hair dyeing on concentrations of methamphetamine and amphetamine in human hairs, Forensic Sci. Int. 206 (1–3) (2011) 77–80. [121] E. Han, M.P. Paulus, M. Wittmann, H. Chung, J.M. Song, Hair analysis and selfreport of methamphetamine use by methamphetamine dependent individuals, J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 879 (7–8) (2011) 541– 547. [122] S. Lee, Y. Park, W. Yang, E. Han, S. Choe, M. Lim, H. Chung, Estimation of the measurement uncertainty of methamphetamine and amphetamine in hair analysis, Forensic Sci. Int. 185 (1–3) (2009) 59–66. [123] A. Kaddoumi, R. Kikura-Hanajiri, K. Nakashima, High-performance liquid chromatography with fluorescence detection for the simultaneous determination of 3,4-methylenedioxymethamphetamine, methamphetamine and their metabolites in human hair using DIB-Cl as a label, Biomed. Chromatogr. 18 (3) (2004) 202–204. [124] J.Y. Kim, S.I. Suh, M.K. In, B.C. Chung, Gas chromatography-high-resolution mass spectrometric method for determination of methamphetamine and its major metabolite amphetamine in human hair, J. Anal. Toxicol. 29 (5) (2005) 370–375. [125] V. Thibert, P. Legeay, F. Chapuis-Hugon, V. Pichon, Synthesis and characterization of molecularly imprinted polymers for the selective extraction of cocaine and its metabolite benzoylecgonine from hair extract before LC–MS analysis, Talanta 88 (2012) 412–419. [126] J.A. Bourland, E.F. Hayes, R.C. Kelly, S.A. Sweeney, M.M. Hatab, Quantitation of cocaine, benzoylecgonine, cocaethylene, methylecgonine and norcocaine in human hair by positive ion chemical ionization (PICI) gas-chromatography– tandem mass spectrometry, J. Anal. Toxicol. 24 (2000) 489–495. [127] M.J. Tabernero, M.L. Felli, A.M. Bermejo, M. Chiarotti, Determination of ketamine and amphetamines in hair by LC/MS/MS, Anal. Bioanal. Chem. 395 (8) (2009) 2547–2557. [128] C. Girod, C. Staub, Methadone and EDDP in hair from human subjects following a maintenance program: results of a pilot study, Forensic Sci. Int. 117 (3) (2001) 175–184.
[129] C. Coulter, J. Tuyay, M. Taruc, C. Moore, Semi-quantitative analysis of drugs of abuse, including tetrahydrocannabinol in hair using aqueous extraction and immunoassay, Forensic Sci. Int. 196 (1–3) (2010) 70–73. [130] R. Kronstrand, I. Nyström, J. Strandberg, H. Druid, Screening for drugs of abuse in hair with ion spray LC–MS–MS, Forensic Sci. Int. 145 (2–3) (2004) 183–190. [131] H. Myyaguchi, Y.T. Iwata, T. kanamori, K. Tsujikawa, K. Kuwayama, H. Inoue, Rapid identification and quantification of methamphetamine and amphetamine in hair by gas chromatography/mass spectrometry coupled with micropulverized extraction, aqueous acetylation and microextraction by packed sorbent, J. Chromatogr. A 1216 (2009) 4063–4070. [132] S. Vogliardi, D. Favretto, G. Frison, S. Maietti, G. Viel, R. Seraglia, P. Traldi, S.D. Ferrara, Validation of a fast screening method for the detection of cocaine in hair by MALDI-MS, Anal. Bioanal. Chem. 396 (7) (2010) 2435–2440. [133] W.E. Brewer, R.C. Galipo, K.W. Sellers, S.L. Morgan, Analysis of cocaine, benzoylecgonine, codeine, and morphine in hair by supercritical fluid extraction with carbon dioxide modified with methanol, Anal. Chem. 73 (2001) 2371–2376. [134] J. Liu, K. Hara, S. Kashimura, M. Kashiwagi, M. Kageura, New method of derivatization and headspace solid-phase microextraction for gas chromatographic–mass spectrometric analysis of amphetamines in hair, J. Chromatogr. B Biomed. Sci. Appl. 758 (2001) 95–101. [135] J.L. Villamor, A.M. Bermejo, P. Fernández, M.J. Tabernero, A new GC–MS method for the determination of five amphetamines in human hair, J. Anal. Toxicol. 29 (2005) 135–139. [136] L.F. Martins, M. Yegles, H. Chung, R. Wennig, Sensitive, rapid and validated gas chromatography/negative ion chemical ionization–mass spectrometry assay including derivatization with a novel chiral agent for the enantioselective quantification of amphetamine-type stimulants in hair, J. Chromatogr. B 842 (2006) 98–105. [137] P. Meng, D. Zhu, H. He, Y. Wang, F. Guo, L. Zhang, Determination of amphetamines in hair by GC/MS after small-volume liquid extraction and microwave derivatization, Anal. Sci. 25 (9) (2009) 1115–1118. [138] H. Sachs, U. Dressler, Detection of THC-COOH in hair by MSD-NCI after HPLC clean-up, Forensic Sci. Int. 107 (2000) 239–247. [139] M. Conti, V. Tazzari, M. Bertona, M. Brambilla, P. Brambilla, Surface-activated chemical ionization combined with electrospray ionization and mass spectrometry for the analysis of cannabinoids in biological samples. Part I: analysis of 11-nor-9-carboxytetrahydro-cannabinol, Rapid Commun. Mass Spectrom. 25 (11) (2011) 1552–1558. [140] M.A. Huestis, R.A. Gustafson, E.T. Moolchan, A. Barnes, J.A. Bourland, S.A. Sweeney, E.F. Hayes, P.M. Carpenter, M.L. Smith, Cannabinoid concentrations in hair from documented cannabis users, Forensic Sci. Int. 169 (2–3) (2007) 129–136. [141] M. Chiarotti, L. Costamagna, Analysis of 11-nor-9-carboxy-delta(9)-tetrahydrocannabinol in biological samples by gas chromatography tandem mass spectrometry (GC/MS-MS), Forensic Sci. Int. 114 (1) (2000) 1–6. [142] F. Sporkert, F. Pragst, Determination of methadone and its metabolites EDDP and EMDP in human hair by headspace solid-phase microextraction and gas chromatography–mass spectrometry, J. Chromatogr. B Biomed. Sci. Appl. 746 (2) (2000) 255–264. [143] M. Míguez-Framil, A. Moreda-Piñeiro, P. Bermejo-Barrera, P. López, M.J. Tabernero, A.M. Bermejo, Improvements on enzymatic hydrolysis of human hair for illicit drug determination by gas chromatography/mass spectrometry, Anal. Chem. 79 (22) (2007) 8564–8570. [144] M.J. Baptista, P.V. Monsanto, E.G. Pinho Marques, A. Bermejo, S. Avila, A.M. Castanheira, C. Margalho, M. Barroso, D.N. Vieira, Hair analysis for delta(9)THC, delta(9)-THC-COOH, CBN and CBD, by GC/MS-EI. Comparison with GC/ MS-NCI for delta(9)-THC-COOH, Forensic Sci. Int. 128 (1–2) (2002) 66–78. [145] M. Míguez-Framil, A. Moreda-Piñeiro, P. Bermejo-Barrera, I. Alvarez-Freire, M.J. Tabernero, A.M. Bermejo, Matrix solid-phase dispersion on column clean-up/pre-concentration as a novel approach for fast isolation of abuse drugs from human hair, J. Chromatogr. A 1217 (41) (2010) 6342–6349. [146] A.M.A. Bermejo, P. Lopez, I. Alvarez, M.J. Tabernero, P. Fernandez, Solid-phase microextraction for the determination of cocaine and cocaethylene in human hair by gas chromatography–mass spectrometry, Forensic Sci. Int. 156 (2006) 2–8. [147] A.M. Bermejo, A.C.S. Lucas, M.J. Tabernero, P. Fernández, Simultaneous determination of methadone, heroin and their metabolites in hair by GC–MS, Anal. Lett. 33 (4) (2000) 739–752. [148] C. Jurado, H. Sachs, Proficiency test for the analysis of hair for drugs of abuse, organized by the Society of Hair Testing, Forensic Sci. Int. 133 (1–2) (2003) 175–178. [149] S. Nakamura, M. Wada, B.L. Crabtree, P.M. Reeves, J.H. Montgomery, H.J. Byrd, S. Harada, N. Kuroda, K. Nakashima, A sensitive semimicro column HPLC method with peroxyoxalate chemiluminescence detection and column switching for determination of MDMA-related compounds in hair, Anal. Bioanal. Chem. 387 (2007) 1983–1990. [150] R. Gottardo, F. Bortolotti, G. De Paoli, J.P. Pascali, I. Miksík, F. Tagliaro, Hair analysis for illicit drugs by using capillary zone electrophoresis-electrospray ionization-ion trap mass spectrometry, J. Chromatogr. A 1159 (1–2) (2007) 185–189. [151] R. Gottardo, A. Fanigliulo, F. Bortolotti, G. De Paoli, J.P. Pascali, F. Tagliaro, Broad-spectrum toxicological analysis of hair based on capillary zone electrophoresis-time-of-flight mass spectrometry, J. Chromatogr. A 1159 (1– 2) (2007) 190–197.
S. Vogliardi et al. / Analytica Chimica Acta 857 (2015) 1–27 [152] M. Concheiro, M. Villain, S. Bouchet, B. Ludes, M. López-Rivadulla, P. Kintz, Windows of detection of tetrazepam in urine, oral fluid, beard, and hair, with a special focus on drug-facilitated crimes, Ther. Drug Monit. 27 (5) (2005) 565–570. [153] P. Kintz, J. Evans, M. Villain, V. Cirimele, Interpretation of hair findings in children after methadone poisoning, Forensic Sci. Int. 196 (1–3) (2010) 51– 54. [154] T. Cairns, V. Hill, M. Schaffer, W. Thistle, Amphetamines in washed hair of demonstrated users and workplace subjects, Forensic Sci. Int. 145 (2–3) (2004) 137–142. [155] C. Girod, C. Staub, Analysis of drugs of abuse in hair by automated solid-phase extraction, GC/EI/MS and GC ion trap/CI/MS, Forensic Sci. Int. 107 (1–3) (2000) 261–271. [156] K.M. Clauwaert, J.F. Van Bocxlaer, W.E. Lambert, A.P. De Leenheer, Segmental analysis for cocaine and metabolites by HPLC in hair of suspected drug overdose cases, Forensic Sci. Int. 110 (3) (2000) 157–166.
27
[157] F. Musshoff, F. Driever, K. Lachenmeier, D.W. Lachenmeier, M. Banger, B. Madea, Results of hair analyses for drugs of abuse and comparison with selfreports and urine tests, Forensic Sci. Int. 156 (2–3) (2006) 118–123. [158] A. Negrusz, C.M. Moore, J.L. Kern, P.G. Janicak, M.J. Strong, N.A. Levy, Quantitation of clonazepam and its major metabolite 7-aminoclonazepam in hair, J. Anal. Toxicol. 24 (7) (2000) 614–620. [159] A.C.S. Lucas, A.M. Bermejo, M.J. Tabernero, P. Fernández, S. Strano-Rossi, Use of solid-phase microextraction (SPME) for the determination of methadone and EDDP in human hair by CG–MS, Forensic Sci. Int. 107 (2000) 225–232. [160] F. Sporkert, F. Pragst, Use of headspace solid-phase microextraction (HS– SPME) in hair analysis for organic compounds, Forensic Sci. Int. 107 (2000) 129–148. [161] J. Yang, Y. Hu, J.B. Cai, X.L. Zhu, Q.D. Su, Y.Q. Hu, F.X. Liang, Selective hair analysis of nicotine by molecular imprinted solid-phase extraction: an application for evaluating tobacco smoke exposure, Food Chem. Toxicol. 45 (6) (2007) 896–903.