Phencyclidine Abuse Clinical Findings and Concentrations in Biological Fluids after Nonfatal Intoxication DAVID N. BAILEY, M.D.
PHENCYCLIDINE ( " P C P , " "angel dust") abuse is being seen in epidemic proportions in many medical centers at the present time, 3 - 5 1 6 and clinical laboratories are frequently called upon to assist with the diagnosis of phencyclidine intoxication. Such laboratory confirmation is particularly important due to the multitude of symptoms that can be seen following phencyclidine usage, many of which may suggest etiologies other than drug ingestion for the grossly altered mental/physical state of the patient. K4,816 Phencyclidine, l-(l-phenylcyclohexyl)piperidine, is metabolized by hydroxylation on the cyclohexane ring to yield 4-phenyl-4-piperidino-cyclohexanol and by hydroxylation on the piperidine moiety to yield 1(l-phenylcyclohexyl)-4-hydroxypiperidine as the maReceived February 28, 1979; received revised manuscript and accepted for publication April 18, 1979. Supported in part by Research Grant MH30943 from the Alcohol, Drug Abuse, and Mental Health Administration, National Institutes of Health, United States Public Health Service. Address reprint requests to Dr. Bailey: Division of Clinical Pathology, University of California Medical Center, 225 W. Dickinson Street, San Diego, California 92103.
Division of Clinical Pathology, University of California Medical Center, 225 W. Dickinson Street, San Diego, California
jor metabolites. Both of these compounds are pharmacologically inactive and are excreted as their glucuronide conjugates in the urine. 18 Despite the increasing abuse of phencyclidine, relatively little is known about concentrations of the compound in the biological fluids of users. This may be due in part to the low /xg/liter (ng/ml) concentrations attained in plasma, 7 1 3 1 4 thereby rendering measurement difficult. Gas-liquid chromatography with flameionization detection has been used for analysis of phencyclidine, 131517 but is too insensitive in most cases to permit detection at the low concentrations frequently seen after casual use of the compound. Mass fragmentography 714 has also been used, but it is usually not available in most clinical laboratories. We recently reported a gas-liquid chromatographic analysis for phencyclidine using a nitrogen detector that is sufficiently sensitive to permit measurement of concentrations as low as 10 /u.g/1.2 We report here the application of this analysis to the plasmas of 22 users of phencyclidine in an attempt to correlate physical findings with plasma levels of the compound and to evaluate the clinical utility of measuring plasma levels of phencyclidine. For seven of the users, phencyclidine concentrations in erythrocytes were also examined and compared with the respective plasma concentrations. In addition, concentrations in 15 unselected specimens of urine were measured and correlated with urinary pH in attempt to evaluate the effect ofpH on the renal excretion of phencyclidine. Materials and Methods Case Finding and Sample
Acquisition
Users of phencyclidine were located by daily review of the qualitative urinary drug-of-abuse screening performed in the Clinical Toxicology Laboratory of the
0002-9173/79/1100/0795 $00.75 © American Society of Clinical Pathologists
795
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Bailey, David N.: Phencyclidine abuse. Clinical findings and concentrations in biological fluids after nonfatal intoxication. Am J Clin Pathol 72: 795-799, 1979. Phencyclidine concentrations were measured in the plasmas of 22 patients with nonfatal phencyclidine intoxication using gas-liquid chromatography with a nitrogen detector. Concentrations found ranged from < 10 to 812 iig/l, and, except for the systolic blood pressure (r = 0.60, P < 0.05), showed no significant correlation with the physical findings. The most common physical findings were combativeness-agitation (64%), depressed level of consciousness (50%), hypertension (43%), miosis (43%), and tachycardia (43%). Phencyclidine concentrations measured in the erythrocytes of seven of the patients were generally higher than concentrations in the corresponding plasmas (erythrocyte:plasma concentration ratios ranged from 3.1 to 37.9), suggesting that the binding of phencyclidine to plasma proteins is low. Erythrocytic concentrations also showed no significant correlation with either the physical findings or the plasma concentrations of phencyclidine. For 15 unselected urines the concentrations of phencyclidine showed no significant correlation with urinary pH. (Key words: Drug abuse; Phencyclidine intoxication; Toxicology.)
796
A.J.C.P. • November 1979
BAILEY
Table 1. Phencyclidine Concentrations in 22 Cases of Nonfatal Intoxication Age (Yr.), Sex Patient Patient Patient Patient Patient
1 2 3 4 5
Patient 6 Patient 7 Patient Patient Patient Patient Patient Patient Patient Patient
8 9 10 11 12 13 14 15
Mode of Ingestion
10/77 10/77 11/77 11/77 12/77
Inhaled Inhaled and Smoked Unknown Inhaled Inhaled
Plasma, Plasma, Plasma, Plasma, Plasma,
2/78 3/78
Unknown Inhaled
Plasma, 183 Plasma, 812
M F F M M M M M
3/78 3/78 5/78 5/78 7/78 7/78 7/78 8/78
Inhaled Unknown Unknown Unknown Unknown Unknown Unknown Unknown
26, F
8/78
Unknown
Plasma, 426 Plasma,
PHENCYCLIDINE ( " P C P , " "angel dust") abuse is being seen in epidemic proportions in many medical centers at the present time, 3 - 5 1 6 and clinical laboratories are frequently called upon to assist with the diagnosis of phencyclidine intoxication. Such laboratory confirmation is particularly important due to the multitude of symptoms that can be seen following phencyclidine usage, many of which may suggest etiologies other than drug ingestion for the grossly altered mental/physical state of the patient. K4,816 Phencyclidine, l-(l-phenylcyclohexyl)piperidine, is metabolized by hydroxylation on the cyclohexane ring to yield 4-phenyl-4-piperidino-cyclohexanol and by hydroxylation on the piperidine moiety to yield 1(l-phenylcyclohexyl)-4-hydroxypiperidine as the maReceived February 28, 1979; received revised manuscript and accepted for publication April 18, 1979. Supported in part by Research Grant MH30943 from the Alcohol, Drug Abuse, and Mental Health Administration, National Institutes of Health, United States Public Health Service. Address reprint requests to Dr. Bailey: Division of Clinical Pathology, University of California Medical Center, 225 W. Dickinson Street, San Diego, California 92103.
Division of Clinical Pathology, University of California Medical Center, 225 W. Dickinson Street, San Diego, California
jor metabolites. Both of these compounds are pharmacologically inactive and are excreted as their glucuronide conjugates in the urine. 18 Despite the increasing abuse of phencyclidine, relatively little is known about concentrations of the compound in the biological fluids of users. This may be due in part to the low /xg/liter (ng/ml) concentrations attained in plasma, 7 1 3 1 4 thereby rendering measurement difficult. Gas-liquid chromatography with flameionization detection has been used for analysis of phencyclidine, 131517 but is too insensitive in most cases to permit detection at the low concentrations frequently seen after casual use of the compound. Mass fragmentography 714 has also been used, but it is usually not available in most clinical laboratories. We recently reported a gas-liquid chromatographic analysis for phencyclidine using a nitrogen detector that is sufficiently sensitive to permit measurement of concentrations as low as 10 /u.g/1.2 We report here the application of this analysis to the plasmas of 22 users of phencyclidine in an attempt to correlate physical findings with plasma levels of the compound and to evaluate the clinical utility of measuring plasma levels of phencyclidine. For seven of the users, phencyclidine concentrations in erythrocytes were also examined and compared with the respective plasma concentrations. In addition, concentrations in 15 unselected specimens of urine were measured and correlated with urinary pH in attempt to evaluate the effect ofpH on the renal excretion of phencyclidine. Materials and Methods Case Finding and Sample
Acquisition
Users of phencyclidine were located by daily review of the qualitative urinary drug-of-abuse screening performed in the Clinical Toxicology Laboratory of the
0002-9173/79/1100/0795 $00.75 © American Society of Clinical Pathologists
795
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 5, 2016
Bailey, David N.: Phencyclidine abuse. Clinical findings and concentrations in biological fluids after nonfatal intoxication. Am J Clin Pathol 72: 795-799, 1979. Phencyclidine concentrations were measured in the plasmas of 22 patients with nonfatal phencyclidine intoxication using gas-liquid chromatography with a nitrogen detector. Concentrations found ranged from < 10 to 812 iig/l, and, except for the systolic blood pressure (r = 0.60, P < 0.05), showed no significant correlation with the physical findings. The most common physical findings were combativeness-agitation (64%), depressed level of consciousness (50%), hypertension (43%), miosis (43%), and tachycardia (43%). Phencyclidine concentrations measured in the erythrocytes of seven of the patients were generally higher than concentrations in the corresponding plasmas (erythrocyte:plasma concentration ratios ranged from 3.1 to 37.9), suggesting that the binding of phencyclidine to plasma proteins is low. Erythrocytic concentrations also showed no significant correlation with either the physical findings or the plasma concentrations of phencyclidine. For 15 unselected urines the concentrations of phencyclidine showed no significant correlation with urinary pH. (Key words: Drug abuse; Phencyclidine intoxication; Toxicology.)
796
A.J.C.P. • November 1979
BAILEY
Table 1. Phencyclidine Concentrations in 22 Cases of Nonfatal Intoxication Age (Yr.), Sex Patient Patient Patient Patient Patient
1 2 3 4 5
Patient 6 Patient 7 Patient Patient Patient Patient Patient Patient Patient Patient
8 9 10 11 12 13 14 15
Mode of Ingestion
10/77 10/77 11/77 11/77 12/77
Inhaled Inhaled and Smoked Unknown Inhaled Inhaled
Plasma, Plasma, Plasma, Plasma, Plasma,
2/78 3/78
Unknown Inhaled
Plasma, 183 Plasma, 812
M F F M M M M M
3/78 3/78 5/78 5/78 7/78 7/78 7/78 8/78
Inhaled Unknown Unknown Unknown Unknown Unknown Unknown Unknown
26, F
8/78
Unknown
Plasma, 426 Plasma,
