Fast and highly selective LC-MS/MS screening for THC and 16 other abused drugs and metabolites in human hair to monitor patients for drug abuse.
BACKGROUND
To facilitate the monitoring of drug abuse by patients, a method was developed and validated for the analysis of amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, methylenedioxyamphetamine, methylenedioxyethylamphetamine, methylphenidate, cocaine, benzoylecgonine, morphine, codeine, heroin, 6-monoacteylmorphine, methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), delta-9-tetrahydrocannabinol (THC), nicotine, and cotinine in human hair.


METHODS
The hair preparation method contains a 3-step wash procedure with dichloromethane followed by a simultaneous hair pulverization and extraction procedure with disposable metal balls. The developed liquid chromatography tandem mass spectrometry method uses a single injection to detect and confirm all 17 abused drugs, including THC, within 4.8 minutes.


RESULTS
Nicotine was validated with a linear range of 800-25,000 pg/mg hair, and all other substances were validated with a linear range of 30.0-2500 pg/mg hair. For inaccuracy and imprecision, the overall bias did not exceed -8.2% and the overall coefficient of variation did not exceed 17.7%. Autosampler stability was proven for 48 hours at 10°C for all substances. Analytical cutoff concentrations were defined for each substance at the lowest validated inaccuracy and imprecision concentration with a bias and coefficient of variation within 15% and qualifier/quantifier ratios within 20% of the set ratio. The analytical cutoff concentrations were 200 pg/mg for codeine and 80.0 pg/mg for 6-MAM, heroin, EDDP, and THC. The analytical cutoff concentration for nicotine was 800 pg/mg and for all other validated substances 30.0 pg/mg. This method was successfully applied to analyze hair samples from patients who were monitored for drug abuse. Hair samples of 47 subjects (segmented into 129 samples) showed 3,4-methylenedioxymethamphetamine, methylphenidate, cocaine, benzoylecgonine, codeine, methadone, EDDP, THC, nicotine, and cotinine above the analytical cutoff.


CONCLUSIONS
The method was fully validated, including the validation of the qualifier/quantifier ratios. The analysis of real hair samples proved the efficacy of the developed method for monitoring drug abuse. The results obtained by this method provide the physician or health-care professional with extensive information about actual drug abuse or relapse and can be used for patient-specific therapy.
*Laboratory for Clinical and Forensic Toxicology and Drugs Analysis, Department of Hospital and Clinical Pharmacy, University of Groningen, University Medical Center Groningen; †SumID-Project, Zorgontwikkeling, Tactus Addiction Medicine, Deventer; and ‡ACSW-Nijmegen Institute for Scientist-Practitioners in Addiction, Radboud University, Nijmegen, The Netherlands.
Remco A
RA
Koster
Jan-Willem C
JW
Alffenaar
Ben
B
Greijdanus
Joanneke E L
JE
VanDernagel
Donald R A
DR
Uges
D002853:Chromatography, Liquid / Q000379:methods*; D013759:Dronabinol / Q000032:analysis* / Q000378:metabolism / Q000493:pharmacokinetics; D006197:Hair / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D013287:Illicit Drugs / Q000032:analysis* / Q000378:metabolism / Q000493:pharmacokinetics; D057230:Limit of Detection; D015813:Substance Abuse Detection / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors
D013287:Illicit Drugs; D013759:Dronabinol