Sensitive gas chromatographic-mass spectrometric screening of acetylated benzodiazepines

GC-MS screening conditions were developed for 15 low-dosed benzodiazepines, covering alprazolam, flunitrazepam, flurazepam, ketazolam, lorazepam and t riazolam, and the corresponding metabolites alpha -hydroxyalprazolam, 4-hyd roxy-alprazolam; 7-aminoflunitrazepam, desmethylflunitrazepam, 7-aminodesme thylflunitrazepam; hydroxyethylflurazepam, N-desalkylflurazepam; oxazepam a nd alpha -hydroxytriazolam, respectively. Benzodiazepines are analyzed on a polydimethylsiloxane column in both the scan and the multiple ion monitori ng modes using on-column injection to attain maximal sensitivity. The react ive compounds are acetylated with pyridine and acetic anhydride for 20 min. The derivatives are stable for at least 4 days. The relative standard devi ation observed with standard compounds at the low nanogram-level ranged fro m 1.13 to 4.87% within-day and from 1.12 to 4.94% between-day. Unequivocal identification potential, high chromatographic resolution and sensitivity a re combined with minimal thermal degradation. The presented screening condi tions provide the basis for a unique routine screening method for low-dosed benzodiazepines with a broad polarity range. (C) 2001 Elsevier Science B.V . All rights reserved.