Simultaneous determinations of a monofluorinated imidazo[1, 5-a][1, 4]benzodiazepine and the corresponding benzophenone as a function of pH and in aqueous formulations by 19F nuclear magnetic resonance spectrometry

8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1, 5-a][1, 4]benzodiazepine (called ''midazolam'') exists in equilibrium with the corresponding benzophenone (the ''open-Mng form''). The two compounds were determined simultaneously as a function of pH with 19F-n.m.r. spectrometry. In a unique application of 19F-n.m.r. spectrometry, the compounds are determined simultaneously in aqueous dosage forms without the need for the lowest concentration of sample used (approximately 1 mg ml-1) was 200:1 for 3000 scans. This was obtained by partial proton decoupling and exponential multiplication of the free induction decay with a line-broadening parameter of 12 Hz. Quantitative results are presented with a standard deviation of < 2.0% in the mean ratio of the two compounds. The results are also compared with those obtained by the spectrophotometric fluorescamine method. Advantages of the 19F-n.m.r. technique in this determination are discussed. (Auth.)