Validated toxicological determination of 30 drugs of abuse as optimized derivatives in oral fluid by long column fast gas chromatography/electron impact mass spectrometry

Abstract

An analytical procedure was developed for the simultaneous sensitive identification, screening and quantitation of 30 drugs of abuse using 250 µl of human oral fluid. The method employs sequential mixed‐mode solid‐phase extraction (SPE), optimized derivative formation and long‐column fast gas chromatography/electron impact mass spectrometry (GC/EI‐MS). After sequential SPE elution, the most sensitive and stable derivatives were formed by taking careful account of the characteristics of the active functional groups and possible steric hindrances affecting derivatization chemistry. Amphetamine‐type stimulant drugs were acylated with heptafluorobutyric anhydride, benzodiazepines and Δ⁹‐tetrahydrocannabinol were silylated with N‐methyl‐N‐(tert‐butyldimethylsilyl)trifluoroacetamide and benzoylecgonine, codeine, ethylmorphine, 6‐monoacetylmorphine, morphine, pholcodine, buprenorphine and norbuprenorphine with N‐methyl‐N‐(trimethylsilyl)trifluoroacetamide. In addition, the following analytes were included: methadone, cocaine, alprazolam, midazolam, fentanyl and zolpidem. In GC separation, fast temperature ramping and high carrier gas flow‐rate combined with long 30 m columns of i.d. 0.32 mm offered a reduction in analysis time and sharp peak shapes while still maintaining sufficient resolution and high sample capacity. Validated parameters including selectivity, linearity, accuracy, intra‐ and inter‐day precision, extraction efficiency and limit of quantitation were all within required limits. In contrast to previously published methods, this single procedure is suitable for the simultaneous toxicological determination of the most common illicit drugs and benzodiazepines, and also zolpidem, in a small amount of oral fluid. Copyright © 2005 John Wiley & Sons, Ltd.