Determination of imidazobenzodiazepine-3-carboxamide, a new anxiolytic agent, in human plasma by gas chromatography--negative chemical-ionization mass spectrometry.
A method is described for measuring imidazobenzodiazepine-3-carboxamide, a new anxiolytic agent, in human plasma. A tetradeuterated analogue of the analyte is used as the internal standard. The drug and its internal standard are (1) extracted from plasma at pH 9 with benzene containing 20% 1,2-dichloroethane, (2) derivatized with pentafluoropropionic anhydride in the presence of triethylamine and (3) the nitrile derivative of the analyte and internal standard are analyzed by gas chromatography (GC)-negative chemical-ionization mass spectrometry (CIMS) using methane as both GC carrier gas and CI reagent gas. The mass spectrometer is set to monitor the intense (M-HCl)- ions of imidazobenzodiazepine-3-nitrile and its tetradeuterated analogue at m/z 316 and m/z 320, respectively. Quantitation of an experimental plasma sample is based on the comparison of the m/z 316 to m/z 320 ion ratio in each sample to that obtained from the analyses of control plasma spiked with various amounts of the drug and a fixed amount of internal standard. The limit of quantitation of the method is approximately 100 pg ml-1 of plasma and the precision (relative standard deviation) at a plasma concentration of 1 ng ml-1 is 4%.
D000328:Adult; D014151:Anti-Anxiety Agents / Q000097:blood*; D001569:Benzodiazepines / Q000097:blood*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D008297:Male; D008874:Midazolam / Q000031:analogs & derivatives*; D009570:Nitriles
D014151:Anti-Anxiety Agents; D009570:Nitriles; D001569:Benzodiazepines; C033415:8-chloro-6-(2-chlorophenyl)-4H-imidazo(1,5-a)(1,4)-benzodiazepine-3-carboxamide; D008874:Midazolam