Determination of the benzodiazepine antagonist Ro 15-1788 in plasma by high-performance liquid chromatography with UV detection.
A sensitive and specific HPLC-assay was developed for the determination of the benzodiazepine antagonist ethyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo-[1,5-a] [1,4]benzodiazepine-3-carboxylate (Ro 15-1788; envisaged INN: flumazepil) in plasma. Ro 15-1788 and the internal standard were extracted from plasma at a basic pH, separated from coextracted plasma components on a reversed-phase column and quantitated by means of a UV detector. Ro 15-1788 was extracted quantitatively from plasma in the concentration range 25.6 to 300 ng/ml. The sensitivity limit was about 10 ng/ml plasma using a 1-ml specimen. The method was shown to be specific with respect to several benzodiazepines and their main metabolites. The method was successfully applied to pharmacokinetic studies in man after oral and intravenous administration of Ro 15-1788.
D001570:Benzodiazepinones / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004355:Drug Stability; D005442:Flumazenil; D006801:Humans; D013056:Spectrophotometry, Ultraviolet / Q000379:methods
D001570:Benzodiazepinones; D005442:Flumazenil