Pharmacokinetics of cocaine and metabolites in human oral fluid and correlation with plasma concentrations after controlled administration.
Oral fluid is an attractive alternative matrix for drug testing with a noninvasive and directly observed collection, but there are few controlled cocaine administration studies to guide interpretation.


METHODS
While residing on a closed research unit for up to 10 weeks under constant medical supervision, 19 participants were administered 75 mg/70 kg subcutaneous cocaine and 14 received 150 mg/70 kg. The disposition of cocaine, benzoylecgonine (BE), and ecgonine methyl ester (EME) into oral fluid was determined by gas chromatography-mass spectrometry for 0.08 to 48 hours after administration.


RESULTS
In oral fluid collected by citric acid candy-stimulated expectoration, cocaine first appeared in oral fluid 0.08 to 0.32 hours after dosing and was rapidly eliminated with half-lives of 1.1 to 3.8 hours. BE and EME were first detected 0.08 to 1.0 hours after dosing with longer half-lives of 3.4 to 13.8 (BE) and 2.4 to 15.5 hours (EME) (P < 0.05). Oral fluid and plasma concentrations were significantly correlated for cocaine, BE, and EME (P < 0.0001). There were no significant differences (P > 0.05) in first and last detection times with the 8-μg/L cutoff proposed by the Substance Abuse and Mental Health Services Administration or the 10-μg/L cutoff from the European initiative, Driving Under the Influence of Drugs, Alcohol and Medicines. Metabolite:cocaine ratios increased after cocaine administration, potentially helpful for interpreting time of last use. Comparison of oral fluid collection through citric acid candy-stimulated expectoration, citric acid-treated Salivette, and neutral cotton Salivette devices did not reveal significant differences between devices for areas under the curve for cocaine, BE, or EME (P > 0.05).


CONCLUSIONS
These results provide additional evidence for interpreting cocaine and metabolite concentrations in oral fluid and oral fluid's usefulness as an alternative matrix for drug testing.
Scheidweiler
Karl B
KB
Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
Spargo
Erin A Kolbrich
EA
Kelly
Tamsin L
TL
Cone
Edward J
EJ
Barnes
Allan J
AJ
Huestis
Marilyn A
MA
D000328:Adult; D019540:Area Under Curve; D003042:Cocaine / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics*; D019970:Cocaine-Related Disorders / Q000175:diagnosis; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005883:Gingival Crevicular Fluid / Q000737:chemistry*; D006207:Half-Life; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D010949:Plasma; D012463:Saliva / Q000737:chemistry*; D013048:Specimen Handling / Q000379:methods; D015813:Substance Abuse Detection / Q000379:methods*
C005618:benzoylecgonine; D003042:Cocaine; C034524:ecgonine methyl ester
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