Citation

Gunnar T, Ariniemi K, Lillsunde PM. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2005; 818(2): 175-189.

Affiliation

National Public Health Institute, Drug Research Unit, Mannerheimintie 166, 00300 Helsinki, Finland. teemu.gunnar@ktl.fi

Copyright

(Copyright © 2005, Elsevier Publishing)

DOI

10.1016/j.jchromb.2004.12.032

PMID

15734157

Abstract

The most common commercially available silylating reagents, N-methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA), N,O-bis-(trimethylsilyl)trifluoroacetamide+1% trimethylchlorosilane (BSTFA+1% TMCS) and N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA) were evaluated to achieve optimal derivatization conditions for analyzing various benzodiazepines based on gas chromatography-electron impact ionization-mass spectrometry (GC-EI-MS). Sensitivity, repeatability, retention times and stability of the derivatives, as well as specificity of mass fragmentation, were studied in detail. Also other parameters affecting the derivatization chemistry of benzodiazepines are discussed. tert-Butyldimethylsilyl (TBDMS) derivatives proved to be more stable, reproducible and sensitive than corresponding trimethylsilyl (TMS) derivatives for the GC-EI-MS analysis of benzodiazepines. Based on the TBDMS derivatives, a rapid, reliable, sensitive and quantitative GC-MS method was developed for the determination of 14 benzodiazepines and two hydroxy metabolites, as well as two non-benzodiazepine hypnotic agents, zolpidem and zaleplon, using 50 microl of whole blood. The method was completely validated in terms of accuracy, intra- and interday precision, limit of detection (LOD), limit of quantitation (LOQ), linearity, selectivity and extraction efficiency; these were all within the required limits, except for the accuracy of nitrazepam at a medium concentration level.

Language: en