Benzodiazepines identified by capillary gas chromatography-mass spectrometry, with specific ion screening used to detect benzophenone derivatives.

Abstract

We developed algorithms for confirmation and identification of benzodiazepines and their metabolites, initially detected in urine samples by enzyme-multiplied immunoassay (EMIT). These algorithms are based on the pattern of benzophenone derivatives of benzodiazepines obtained by gas chromatography-mass spectrometry (GC-MS) with use of a modified specific ion selection mode. Benzophenone derivatives were produced by acid hydrolysis of urine samples containing benzodiazepines and (or) their metabolites. We present mass spectra of the newer benzodiazepines--alprazolam, midazolam, and triazolam--and we determined the detection limit (0.2 mg/L) for these drugs as measured with the EMIT d.a.u. benzodiazepine assay and the ETS instrument (both from Syva Co.). We conclude that these algorithms are useful mostly in forensic toxicology in which unequivocal identification of benzodiazepines is the desired goal.

Forensic science

“…Eleven benzodiazepines were separated by using supercritical fluid chromatography on columns packed with polystyrene-divinylbenzene and ODSand cyano-honded silica (275). Alogrithms based on the pattern of benzophenone derivatives of benzodiazepines obtained by GC/MS were used to confirm and identify benzodiazepines and their metabolites initially detected in urine by EMIT (276). Microcolumn cleanup and HPLC/ECD have been used to determine benzodiazepines in contaminated and degraded blood samples (277).…”

Determination of 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine by adsorptive stripping with pulse voltammetry

“…The fused imidazole ring of midazolam confers on the molecule an increased stability to hydrolysis compared with other benzodiazepines (2).The large number of published analytical methods for determination of midazolam shows the current interest in this compound. There are available a number of gas chromatographic methods with EC (3-18), NSD (19-21), or MS (3,14,20,(22)(23)(24)(25)(26) detection, liquid chromatography with UV (3, 20, 22, 27-33) detection, immunoassays (2, 24, 34-39), thin-layer chromatography (27,37,40), potentiometric acid-base titration (41), fluorine nuclear magnetic resonance (42), spectrophotometry (43, 44), and differential pulse polarography (DPP) 0003-2700/90/0362-2632Í02.50/0 without (45-47) and with (48) adsorptive preconcentration. The latter has also been applied to the determination of the urinary metabolite, the 1-hydroxymethyl derivative of midazolam (18).…”