528176 research-article2014
VDIXXX10.1177/1040638714528176Detection of terbufos using DESI mass spectrometryWilson et al.
Brief Research Report
Rapid detection of terbufos in stomach contents using desorption electrospray ionization mass spectrometry
Journal of Veterinary Diagnostic Investigation 2014, Vol. 26(3) 428–430 © 2014 The Author(s) Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1040638714528176 jvdi.sagepub.com
Christina R. Wilson,1 Christopher C. Mulligan, Kurt D. Strueh, Gregory W. Stevenson, Stephen B. Hooser
Abstract. Desorption electrospray ionization mass spectrometry (DESI-MS) is an emerging analytical technique that permits the rapid and direct analysis of biological or environmental samples under ambient conditions. Highlighting the versatility of this technique, DESI-MS has been used for the rapid detection of illicit drugs, chemical warfare agents, agricultural chemicals, and pharmaceuticals from a variety of sample matrices. In diagnostic veterinary toxicology, analyzing samples using traditional analytical instrumentation typically includes extensive sample extraction procedures, which can be time consuming and labor intensive. Therefore, efforts to expedite sample analyses are a constant goal for diagnostic toxicology laboratories. In the current report, DESI-MS was used to directly analyze stomach contents from a dog exposed to the organophosphate insecticide terbufos. The total DESI-MS analysis time required to confirm the presence of terbufos and diagnose organophosphate poisoning in this case was approximately 5 min. This highlights the potential of this analytical technique in the field of veterinary toxicology for the rapid diagnosis and detection of toxicants in biological samples. Key words: Ambient mass spectrometry; desorption electrospray ionization; toxicology.
Desorption electrospray ionization (DESI) is an ionization technique developed for detection of chemicals by mass spectrometry (MS) under ambient conditions.18 Because ionization with DESI-MS occurs in an ambient environment, samples being tested are directly analyzed with little to no prior sample pretreatment. This technique is applicable for the analysis of a variety of biological matrices, and other liquid or solid media, and is capable of near instantaneous detection of chemicals with a high degree of sensitivity. Rapid and accurate detection of alkaloids, anabolic steroids, agricultural chemicals, explosives, illicit drugs, and pharmaceuticals in a variety of sample matrices are a few examples of the versatility of this technique.3,8,10,12,17–20 In diagnostic veterinary toxicology, extraction of complex biological matrices, when coupled with the analysis times required for traditional analytical instrumentation, can be time consuming and labor intensive. The duration of time between sample submission and reporting toxicology results can have implications on the rapidity of treatment or on remedial efforts to eliminate toxicant exposure in other animals or people. Therefore, efforts to improve extraction efficiency and decrease analysis times in order to expedite diagnoses are a constant goal for diagnostic toxicology laboratories. The current report describes the use of DESI-MS in expediting sample analysis and toxicology results in a case of terbufos poisoning.
Three dogs from the same residence were involved in the current case; 2 of the dogs were found dead and 1 was admitted to the Frankfort Animal Hospital (Frankfort, Indiana). According to the case history, 2 days prior there was a field application of an organophosphate insecticide, suspected to be terbufos, near the residence. After being applied to a field, it was suspected that the dogs had access to a central location in which the insecticide had collected due to runoff after a long rain in that area. The surviving 1-year-old, male pit bull presented at the clinic with hypersalivation, miosis, and muscle fasciculations. Although the dog was treated aggressively with fluid therapy, atropine, phenobarbital, and diazepam, it died within 24 hr after being admitted to the animal hospital. One of the other 2 deceased dogs, an 8-month-old, female mixed breed, was submitted for postmortem examination to the Animal Disease Diagnostic Laboratory at Purdue From the Department of Comparative Pathobiology, School of Veterinary Medicine (Wilson, Hooser), and Animal Disease Diagnostic Laboratory (Wilson, Hooser), Purdue University, West Lafayette, IN; Department of Chemistry, Illinois State University, Normal, IL (Mulligan); Frankfort Animal Hospital, Frankfort, IN (Strueh); and Veterinary Diagnostic & Production Animal Medicine, Ames, IA (Stevenson). 1
Corresponding Author: Christina R. Wilson, Animal Disease Diagnostic Laboratory, Purdue University, 406 South University Street, West Lafayette, IN 47907. [email protected]
Downloaded from vdi.sagepub.com at UNIV OF MICHIGAN on March 13, 2015
Detection of terbufos using DESI mass spectrometry University (West Lafayette, Indiana). At necropsy, lesions consistent with cause of death were not apparent on gross examination. Significant gross lesions were not observed in the tissues of the integumentary, musculoskeletal, respiratory, genital, urinary, lymphatic, endocrine, and nervous systems. Tissues including liver, lung, spleen, thymus, and small intestine were fixed in 10% neutral buffered formalin and submitted for histology. Histologic examination of multiple organs revealed diffuse congestion. The brain and stomach contents were submitted for toxicology testing. Duplicate samples of homogenized brain tissue were prepared using a modification of the Ellman colorimetric assay for acetylcholinesterase activity.4,6 The replicates were analyzed using a spectrophotometer,a and the cholinesterase activity was reported as µm/g/min. The mean brain cholinesterase activity in the mixed-breed dog was 1.02 μm/g/min, which is approximately 26% of the normal mean cholinesterase value in canine brain. In diagnostic toxicology cases, depression of enzyme activity greater than 50% is considered indicative of potential exposure to an anticholinesterase agent.1 Therefore, in the current case, the brain cholinesterase activity was depressed by 74%, suggesting that the dog was potentially exposed to an anticholinesterase agent, such as an organophosphate or carbamate insecticide. A small subsample (approximately 0.1 g) of the stomach contents from this dog was applied to filter paper and directly analyzed by DESIb-MS.c The DESI parameters utilized for this experiment were similar to those commonly reported in the literature,18 which included a solvent flow rate (1:1, methanol:water) of 3.0 µl/min, spray angle of 45°, and a nebulizing nitrogen gas pressure of 120 psi. Spectral data was collected using an average of 5 µscans/MS scan and an ionization time of 250 msec. Protonated molecules of terbufos (m/z 289) and terbufos sulfoxide (m/z 305) were readily detected in the stomach content subsample (Fig. 1A). Corresponding tandem mass spectrometry (MS/MS) analysis of the terbufos precursor ion m/z 289 resulted in characteristic fragment ions at m/z 103 and m/z 233 (Fig. 1B), thereby providing positive confirmation of terbufos in the stomach contents. Both precursor and fragment ions observed using this technique were consistent with other methods reported in the literature for terbufos and terbufos sulfoxide.7,16 The total DESI-MS analysis time required to confirm the presence of terbufos and diagnose organophosphate poisoning in the present case was approximately 5 min; whereas, the use of other traditional analytical techniques would have required several hours of sample preparation and analysis time before reaching a diagnosis. For example, gas chromatography– mass spectrometry (GC-MS) was also used to confirm the presence of terbufos in the stomach contents sample from this case. The total sample preparation and analysis time required to confirm terbufos was approximately 6 hr. However, it is important to note that while the DESI-MS technique provides a rapid means for confirming the presence of toxicants, such as terbufos, it is a qualitative diagnostic
429
Figure 1. Positive ion desorption electrospray ionization mass spectrum of stomach contents. A, [M + H]+ ions characteristic of terbufos and terbufos sulfoxide were detected at m/z 289 and m/z 305, respectively. B, tandem mass spectrometry spectrum of the terbufos precursor ion at m/z 289. Distinctive terbufos fragment ions were detected at m/z 103 and m/z 233.
method. Therefore, detection of toxicants using this technique may warrant subsequent analyses using more quantitative methods of analysis. Using DESI-MS, the ability to directly analyze the stomach contents from this case enabled rapid detection and diagnosis of terbufos poisoning. Terbufos is an organophosphorus insecticide that is widely used in agriculture and industry to control pests such as corn rootworm, nematodes, seed corn maggots, and white grubs.21 The toxicity of terbufos and other organophosphate insecticides is through acetylcholinesterase inhibition, which results in accumulation of acetylcholine at nerve synapses causing overstimulation of muscarinic, nicotinic, and central nervous system cholinergic receptors. Because these cholinergic receptors are present in both insects and mammals, accidental or malicious poisonings in nontarget species often occur and are of toxicological concern in both human and veterinary medicine.2,5,11,15,22 Traditional analytical toxicology methodologies typically employed to diagnose insecticide poisoning in these cases include GC–electron capture detection, GC– nitrogen phosphorus detection, GC-MS/MS, and liquid chromatography–MS/MS.9,13,14,23 While these analytical techniques produce accurate results, the sample preparation and analysis times are labor intensive and time consuming, requiring up to several hours before a diagnosis can be achieved. Because of the toxicological implications in cases where nontarget species are exposed to organophosphate insecticides, rapid detection and diagnosis of exposure is of
Downloaded from vdi.sagepub.com at UNIV OF MICHIGAN on March 13, 2015
430
Wilson et al.
utmost importance. DESI-MS accomplishes this through direct analysis of biological samples for a variety of toxicants and drugs, while providing high sensitivity and instantaneous analysis times. The current diagnostic case highlights the potential application of DESI-MS in the field of veterinary toxicology through rapid diagnosis and detection of toxins and toxicants in biological samples. Sources and manufacturers a. 8452A diode array spectrophotometer, Hewlett-Packard, Palo Alto, CA. b. OmniSpray ion source, Prosolia Inc., Indianapolis, IN. c. LTQ ion trap mass spectrometer, Thermo-Finnigan, Waltham, MA.
Declaration of conflicting interests The author(s) declared no potential conflicts of interest with respect to research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for this research, authorship, and/or publication of this article.
References 1. Arrieta DE, McCurdy SA, Henderson JD, et al.: 2009, Normal range of human red blood cell acetylcholinesterase activity. Drug Chem Toxicol 32:182–185. 2. Balme KH, Roberts JC, Glasstone M, et al.: 2010, Pesticide poisonings at a tertiary children’s hospital in South Africa: an increasing problem. Clin Toxicol (Phila) 48:928–934. 3. Campbell IS, Ton AT, Mulligan CC: 2011, Direct detection of pharmaceuticals and personal care products from aqueous samples with thermally-assisted desorption electrospray ionization mass spectrometry. J Am Soc Mass Spectrom 22:1285–1293. 4. Ellman GL, Courtney KD, Andres V Jr, Featherstone RM: 1961, A new and rapid calorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–90, IN1, 91–95. 5. Gupta RC: 2007, Organophosphates and carbamates. In: Veterinary toxicology, ed. Gupta RC, pp. 477–493. Elsevier, New York, NY. 6. Harlin KS, Hamdy S, Beasley VR: 1989, Preliminary studies with bovine retina cholinesterase determinations in organophosphorus insecticide poisoning. J Vet Diagn Invest 1:356–358 7. Hertherton CL, Sykes MD, Fussell RJ, Goodall DM: 2004, A multi-residue screening method for the determination of 73 pesticides and metabolites in fruit and vegetables using highperformance liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 18:2443–2450. 8. Huang G, Chen H, Zhang X, et al.: 2007, Rapid screening of anabolic steroids in urine by reactive desorption electrospray ionization. Anal Chem 79:8327–8332.
9. Khummueng W, Morrison P, Marriott PJ: 2008, Dual NPD/ECD detection in comprehensive two-dimensional gas chromatography for multiclass pesticide analysis. J Sep Sci 31:3404–3415. 10. Leuthold LA, Mandscheff JF, Fathi M, et al.: 2006, Desorption electrospray ionization mass spectrometry: direct toxicological screening and analysis of illicit Ecstasy tablets. Rapid Commun Mass Spectrom 20:103–110. 11. Mackenzie Ross SJ, Brewin CR, Curran HV, et al.: 2010, Neuropsychological and psychiatric functioning in sheep farmers exposed to low levels of organophosphate pesticides. Neurotoxicol Teratol 32:452–459. 12. Mulligan CC, MacMillan DK, Noll RJ, Cooks RG: 2007, Fast analysis of high-energy compounds and agricultural chemicals in water with desorption electrospray ionization mass spectrometry. Rapid Commun Mass Spectrom 21:3729–3736. 13. Pang GF, Cao YZ, Fan CL, et al.: 2009, Analysis method study on 839 pesticide and chemical contaminant multiresidues in animal muscles by gel permeation chromatography cleanup, GC/MS, and LC/MS/MS. J AOAC Int 92:933–940. 14. Park MJ, In SW, Lee SK, et al.: 2009, Postmortem blood concentrations of organophosphorus pesticides. Forensic Sci Int 184:28–31. 15. Peter JV, Jerobin J, Nair A, et al.: 2010, Clinical profile and outcome of patients hospitalized with dimethyl and diethyl organophosphate poisoning. Clin Toxicol (Phila) 48: 916–923. 16. Stout SJ, daCunha AR, Boyd JE, Devine JM: 1989, Confirmation of phorate, terbufos, and their sulfoxides and sulfones in water by capillary gas chromatography/chemical ionization mass spectrometry. J Assoc Off Anal Chem 72:987–991. 17. Takáts Z, Cotte-Rodriguez I, Talaty N, et al.: 2005, Direct, trace level detection of explosives on ambient surfaces by desorption electrospray ionization mass spectrometry. Chem Commun (Camb) 1950–1952. 18. Takáts Z, Wiseman JM, Gologan B, Cooks RG: 2004, Mass spectrometry sampling under ambient conditions with desorption electrospray ionization. Science 306:471–473. 19. Talaty N, Mulligan CC, Justes DR, et al.: 2008, Fabric analysis by ambient mass spectrometry for explosives and drugs. Analyst 133:1532–1540. 20. Talaty N, Takáts Z, Cooks RG: 2005, Rapid in situ detection of alkaloids in plant tissue under ambient conditions using desorption electrospray ionization. Analyst 130:1624–1633. 21. Thomson WT: 2001, Organic phosphates: dithiophosphate prototypes. In: Agricultural chemicals, book I—insecticides, acaricides and ovicides, ed. Thomson WT, p. 224. Thomson Publications, Fresno, CA. 22. Villar D, Balvin D, Giraldo C, et al.: 2010, Plasma and brain cholinesterase in methomyl-intoxicated free-ranging pigeons (Columba livia f. domestica). J Vet Diagn Invest 22:313–315. 23. Wang Y, Du R: 2010, Simultaneous extraction of trace organophosphorous pesticides from plasma sample by automated solid phase extraction and determination by gas chromatography coupled with pulsed flame photometric detector. Forensic Sci Int 198:70–73.
Downloaded from vdi.sagepub.com at UNIV OF MICHIGAN on March 13, 2015
VDIXXX10.1177/1040638714528176Detection of terbufos using DESI mass spectrometryWilson et al.
Brief Research Report
Rapid detection of terbufos in stomach contents using desorption electrospray ionization mass spectrometry
Journal of Veterinary Diagnostic Investigation 2014, Vol. 26(3) 428–430 © 2014 The Author(s) Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1040638714528176 jvdi.sagepub.com
Christina R. Wilson,1 Christopher C. Mulligan, Kurt D. Strueh, Gregory W. Stevenson, Stephen B. Hooser
Abstract. Desorption electrospray ionization mass spectrometry (DESI-MS) is an emerging analytical technique that permits the rapid and direct analysis of biological or environmental samples under ambient conditions. Highlighting the versatility of this technique, DESI-MS has been used for the rapid detection of illicit drugs, chemical warfare agents, agricultural chemicals, and pharmaceuticals from a variety of sample matrices. In diagnostic veterinary toxicology, analyzing samples using traditional analytical instrumentation typically includes extensive sample extraction procedures, which can be time consuming and labor intensive. Therefore, efforts to expedite sample analyses are a constant goal for diagnostic toxicology laboratories. In the current report, DESI-MS was used to directly analyze stomach contents from a dog exposed to the organophosphate insecticide terbufos. The total DESI-MS analysis time required to confirm the presence of terbufos and diagnose organophosphate poisoning in this case was approximately 5 min. This highlights the potential of this analytical technique in the field of veterinary toxicology for the rapid diagnosis and detection of toxicants in biological samples. Key words: Ambient mass spectrometry; desorption electrospray ionization; toxicology.
Desorption electrospray ionization (DESI) is an ionization technique developed for detection of chemicals by mass spectrometry (MS) under ambient conditions.18 Because ionization with DESI-MS occurs in an ambient environment, samples being tested are directly analyzed with little to no prior sample pretreatment. This technique is applicable for the analysis of a variety of biological matrices, and other liquid or solid media, and is capable of near instantaneous detection of chemicals with a high degree of sensitivity. Rapid and accurate detection of alkaloids, anabolic steroids, agricultural chemicals, explosives, illicit drugs, and pharmaceuticals in a variety of sample matrices are a few examples of the versatility of this technique.3,8,10,12,17–20 In diagnostic veterinary toxicology, extraction of complex biological matrices, when coupled with the analysis times required for traditional analytical instrumentation, can be time consuming and labor intensive. The duration of time between sample submission and reporting toxicology results can have implications on the rapidity of treatment or on remedial efforts to eliminate toxicant exposure in other animals or people. Therefore, efforts to improve extraction efficiency and decrease analysis times in order to expedite diagnoses are a constant goal for diagnostic toxicology laboratories. The current report describes the use of DESI-MS in expediting sample analysis and toxicology results in a case of terbufos poisoning.
Three dogs from the same residence were involved in the current case; 2 of the dogs were found dead and 1 was admitted to the Frankfort Animal Hospital (Frankfort, Indiana). According to the case history, 2 days prior there was a field application of an organophosphate insecticide, suspected to be terbufos, near the residence. After being applied to a field, it was suspected that the dogs had access to a central location in which the insecticide had collected due to runoff after a long rain in that area. The surviving 1-year-old, male pit bull presented at the clinic with hypersalivation, miosis, and muscle fasciculations. Although the dog was treated aggressively with fluid therapy, atropine, phenobarbital, and diazepam, it died within 24 hr after being admitted to the animal hospital. One of the other 2 deceased dogs, an 8-month-old, female mixed breed, was submitted for postmortem examination to the Animal Disease Diagnostic Laboratory at Purdue From the Department of Comparative Pathobiology, School of Veterinary Medicine (Wilson, Hooser), and Animal Disease Diagnostic Laboratory (Wilson, Hooser), Purdue University, West Lafayette, IN; Department of Chemistry, Illinois State University, Normal, IL (Mulligan); Frankfort Animal Hospital, Frankfort, IN (Strueh); and Veterinary Diagnostic & Production Animal Medicine, Ames, IA (Stevenson). 1
Corresponding Author: Christina R. Wilson, Animal Disease Diagnostic Laboratory, Purdue University, 406 South University Street, West Lafayette, IN 47907. [email protected]
Downloaded from vdi.sagepub.com at UNIV OF MICHIGAN on March 13, 2015
Detection of terbufos using DESI mass spectrometry University (West Lafayette, Indiana). At necropsy, lesions consistent with cause of death were not apparent on gross examination. Significant gross lesions were not observed in the tissues of the integumentary, musculoskeletal, respiratory, genital, urinary, lymphatic, endocrine, and nervous systems. Tissues including liver, lung, spleen, thymus, and small intestine were fixed in 10% neutral buffered formalin and submitted for histology. Histologic examination of multiple organs revealed diffuse congestion. The brain and stomach contents were submitted for toxicology testing. Duplicate samples of homogenized brain tissue were prepared using a modification of the Ellman colorimetric assay for acetylcholinesterase activity.4,6 The replicates were analyzed using a spectrophotometer,a and the cholinesterase activity was reported as µm/g/min. The mean brain cholinesterase activity in the mixed-breed dog was 1.02 μm/g/min, which is approximately 26% of the normal mean cholinesterase value in canine brain. In diagnostic toxicology cases, depression of enzyme activity greater than 50% is considered indicative of potential exposure to an anticholinesterase agent.1 Therefore, in the current case, the brain cholinesterase activity was depressed by 74%, suggesting that the dog was potentially exposed to an anticholinesterase agent, such as an organophosphate or carbamate insecticide. A small subsample (approximately 0.1 g) of the stomach contents from this dog was applied to filter paper and directly analyzed by DESIb-MS.c The DESI parameters utilized for this experiment were similar to those commonly reported in the literature,18 which included a solvent flow rate (1:1, methanol:water) of 3.0 µl/min, spray angle of 45°, and a nebulizing nitrogen gas pressure of 120 psi. Spectral data was collected using an average of 5 µscans/MS scan and an ionization time of 250 msec. Protonated molecules of terbufos (m/z 289) and terbufos sulfoxide (m/z 305) were readily detected in the stomach content subsample (Fig. 1A). Corresponding tandem mass spectrometry (MS/MS) analysis of the terbufos precursor ion m/z 289 resulted in characteristic fragment ions at m/z 103 and m/z 233 (Fig. 1B), thereby providing positive confirmation of terbufos in the stomach contents. Both precursor and fragment ions observed using this technique were consistent with other methods reported in the literature for terbufos and terbufos sulfoxide.7,16 The total DESI-MS analysis time required to confirm the presence of terbufos and diagnose organophosphate poisoning in the present case was approximately 5 min; whereas, the use of other traditional analytical techniques would have required several hours of sample preparation and analysis time before reaching a diagnosis. For example, gas chromatography– mass spectrometry (GC-MS) was also used to confirm the presence of terbufos in the stomach contents sample from this case. The total sample preparation and analysis time required to confirm terbufos was approximately 6 hr. However, it is important to note that while the DESI-MS technique provides a rapid means for confirming the presence of toxicants, such as terbufos, it is a qualitative diagnostic
429
Figure 1. Positive ion desorption electrospray ionization mass spectrum of stomach contents. A, [M + H]+ ions characteristic of terbufos and terbufos sulfoxide were detected at m/z 289 and m/z 305, respectively. B, tandem mass spectrometry spectrum of the terbufos precursor ion at m/z 289. Distinctive terbufos fragment ions were detected at m/z 103 and m/z 233.
method. Therefore, detection of toxicants using this technique may warrant subsequent analyses using more quantitative methods of analysis. Using DESI-MS, the ability to directly analyze the stomach contents from this case enabled rapid detection and diagnosis of terbufos poisoning. Terbufos is an organophosphorus insecticide that is widely used in agriculture and industry to control pests such as corn rootworm, nematodes, seed corn maggots, and white grubs.21 The toxicity of terbufos and other organophosphate insecticides is through acetylcholinesterase inhibition, which results in accumulation of acetylcholine at nerve synapses causing overstimulation of muscarinic, nicotinic, and central nervous system cholinergic receptors. Because these cholinergic receptors are present in both insects and mammals, accidental or malicious poisonings in nontarget species often occur and are of toxicological concern in both human and veterinary medicine.2,5,11,15,22 Traditional analytical toxicology methodologies typically employed to diagnose insecticide poisoning in these cases include GC–electron capture detection, GC– nitrogen phosphorus detection, GC-MS/MS, and liquid chromatography–MS/MS.9,13,14,23 While these analytical techniques produce accurate results, the sample preparation and analysis times are labor intensive and time consuming, requiring up to several hours before a diagnosis can be achieved. Because of the toxicological implications in cases where nontarget species are exposed to organophosphate insecticides, rapid detection and diagnosis of exposure is of
Downloaded from vdi.sagepub.com at UNIV OF MICHIGAN on March 13, 2015
430
Wilson et al.
utmost importance. DESI-MS accomplishes this through direct analysis of biological samples for a variety of toxicants and drugs, while providing high sensitivity and instantaneous analysis times. The current diagnostic case highlights the potential application of DESI-MS in the field of veterinary toxicology through rapid diagnosis and detection of toxins and toxicants in biological samples. Sources and manufacturers a. 8452A diode array spectrophotometer, Hewlett-Packard, Palo Alto, CA. b. OmniSpray ion source, Prosolia Inc., Indianapolis, IN. c. LTQ ion trap mass spectrometer, Thermo-Finnigan, Waltham, MA.
Declaration of conflicting interests The author(s) declared no potential conflicts of interest with respect to research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for this research, authorship, and/or publication of this article.
References 1. Arrieta DE, McCurdy SA, Henderson JD, et al.: 2009, Normal range of human red blood cell acetylcholinesterase activity. Drug Chem Toxicol 32:182–185. 2. Balme KH, Roberts JC, Glasstone M, et al.: 2010, Pesticide poisonings at a tertiary children’s hospital in South Africa: an increasing problem. Clin Toxicol (Phila) 48:928–934. 3. Campbell IS, Ton AT, Mulligan CC: 2011, Direct detection of pharmaceuticals and personal care products from aqueous samples with thermally-assisted desorption electrospray ionization mass spectrometry. J Am Soc Mass Spectrom 22:1285–1293. 4. Ellman GL, Courtney KD, Andres V Jr, Featherstone RM: 1961, A new and rapid calorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–90, IN1, 91–95. 5. Gupta RC: 2007, Organophosphates and carbamates. In: Veterinary toxicology, ed. Gupta RC, pp. 477–493. Elsevier, New York, NY. 6. Harlin KS, Hamdy S, Beasley VR: 1989, Preliminary studies with bovine retina cholinesterase determinations in organophosphorus insecticide poisoning. J Vet Diagn Invest 1:356–358 7. Hertherton CL, Sykes MD, Fussell RJ, Goodall DM: 2004, A multi-residue screening method for the determination of 73 pesticides and metabolites in fruit and vegetables using highperformance liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 18:2443–2450. 8. Huang G, Chen H, Zhang X, et al.: 2007, Rapid screening of anabolic steroids in urine by reactive desorption electrospray ionization. Anal Chem 79:8327–8332.
9. Khummueng W, Morrison P, Marriott PJ: 2008, Dual NPD/ECD detection in comprehensive two-dimensional gas chromatography for multiclass pesticide analysis. J Sep Sci 31:3404–3415. 10. Leuthold LA, Mandscheff JF, Fathi M, et al.: 2006, Desorption electrospray ionization mass spectrometry: direct toxicological screening and analysis of illicit Ecstasy tablets. Rapid Commun Mass Spectrom 20:103–110. 11. Mackenzie Ross SJ, Brewin CR, Curran HV, et al.: 2010, Neuropsychological and psychiatric functioning in sheep farmers exposed to low levels of organophosphate pesticides. Neurotoxicol Teratol 32:452–459. 12. Mulligan CC, MacMillan DK, Noll RJ, Cooks RG: 2007, Fast analysis of high-energy compounds and agricultural chemicals in water with desorption electrospray ionization mass spectrometry. Rapid Commun Mass Spectrom 21:3729–3736. 13. Pang GF, Cao YZ, Fan CL, et al.: 2009, Analysis method study on 839 pesticide and chemical contaminant multiresidues in animal muscles by gel permeation chromatography cleanup, GC/MS, and LC/MS/MS. J AOAC Int 92:933–940. 14. Park MJ, In SW, Lee SK, et al.: 2009, Postmortem blood concentrations of organophosphorus pesticides. Forensic Sci Int 184:28–31. 15. Peter JV, Jerobin J, Nair A, et al.: 2010, Clinical profile and outcome of patients hospitalized with dimethyl and diethyl organophosphate poisoning. Clin Toxicol (Phila) 48: 916–923. 16. Stout SJ, daCunha AR, Boyd JE, Devine JM: 1989, Confirmation of phorate, terbufos, and their sulfoxides and sulfones in water by capillary gas chromatography/chemical ionization mass spectrometry. J Assoc Off Anal Chem 72:987–991. 17. Takáts Z, Cotte-Rodriguez I, Talaty N, et al.: 2005, Direct, trace level detection of explosives on ambient surfaces by desorption electrospray ionization mass spectrometry. Chem Commun (Camb) 1950–1952. 18. Takáts Z, Wiseman JM, Gologan B, Cooks RG: 2004, Mass spectrometry sampling under ambient conditions with desorption electrospray ionization. Science 306:471–473. 19. Talaty N, Mulligan CC, Justes DR, et al.: 2008, Fabric analysis by ambient mass spectrometry for explosives and drugs. Analyst 133:1532–1540. 20. Talaty N, Takáts Z, Cooks RG: 2005, Rapid in situ detection of alkaloids in plant tissue under ambient conditions using desorption electrospray ionization. Analyst 130:1624–1633. 21. Thomson WT: 2001, Organic phosphates: dithiophosphate prototypes. In: Agricultural chemicals, book I—insecticides, acaricides and ovicides, ed. Thomson WT, p. 224. Thomson Publications, Fresno, CA. 22. Villar D, Balvin D, Giraldo C, et al.: 2010, Plasma and brain cholinesterase in methomyl-intoxicated free-ranging pigeons (Columba livia f. domestica). J Vet Diagn Invest 22:313–315. 23. Wang Y, Du R: 2010, Simultaneous extraction of trace organophosphorous pesticides from plasma sample by automated solid phase extraction and determination by gas chromatography coupled with pulsed flame photometric detector. Forensic Sci Int 198:70–73.
Downloaded from vdi.sagepub.com at UNIV OF MICHIGAN on March 13, 2015
