Analysis of the metabolites of ethyl loflazepate by gas chromatography with electron-capture detection.
A gas chromatographic assay with electron-capture detection (GC--EC) is described for the metabolites of ethyl loflazepate (Victan), a new benzodiazepine with a potent anti-anxiety activity, in biological fluids. Since the parent drug undergoes a first-pass effect, pharmacokinetic data may only be obtained by measuring the total levels of two of the major metabolites. Accurate data can not be obtained for the metabolites separately since one of them (M1) is chemically transformed to the other (M2) during plasma sampling, storage and extraction. A sensitive, specific and accurate GC--EC assay is developed using a synthetic analogue of M2 as an internal standard. The limit of detection in plasma is approximately 2 ng/ml and the precision about 3% (within-run and between-run). The method is applied to plasma samples collected after oral administration of 2 mg and 4 mg of the drug in tablet form to human volunteers. The results obtained are correlated with those from an existing gas chromatographic--mass spectrometric assay. A very good correlation between the results (inter-laboratory comparison) is obtained, validating both techniques.
D014151:Anti-Anxiety Agents / Q000378:metabolism*; D001569:Benzodiazepines; D001570:Benzodiazepinones / Q000378:metabolism*; D002849:Chromatography, Gas / Q000379:methods; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007700:Kinetics; D013997:Time Factors
D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D001569:Benzodiazepines; C029617:ethyl loflazepate