Electron capture and multiple ion detection of benzodiazepine esters in pharmacokinetic studies.
A sensitive and highly specific gas-liquid chromatographic method is described for the determination of benzodiazepine esters. The method involves the extraction of pivoxazepam and 2'-chloropivoxazepam from blood and urine samples and the hydrolysis of both drugs with strong acid to the corresponding 2-amino-5-chlorobenzophenone (ACB) and 2-amino-5,2'-dichlorobenzophenone (ACDB). Recoveries of 97-98% have been obtained and the trifluoroacetic (TFA) derivatives of both benzophenones (ACB-TFA and ACDB-TFA) can be chromatographed on OV-17, in a short time, with good electron-capture detector (ECD) responses. The mass spectra of these derivatives provide abundant molecular ions suitable for mass spectrometric detection by multiple ion detection (MID),  with a considerable improvement in specificity compared with the ECD responses. The detection limits in blood specimens have been established at 5-10 ng/ml by ECD and 0.5-0.8 ng/ml by MID. The method has been applied to the study of blood levels attained after i.v. and oral doses in rats and in man.
Electron capture and multiple ion detection of benzodiazepine esters in pharmacokinetic studies. A sensitive and highly specific gas-liquid chromatographic method is described for the determination of benzodiazepine esters. The method involves the extraction of pivoxazepam and 2'-chloropivoxazepam from blood and urine samples and the hydrolysis of both drugs with strong acid to the corresponding 2-amino-5-chlorobenzophenone (ACB) and 2-amino-5,2'-dichlorobenzophenone (ACDB). Recoveries of 97-98% have been obtained and the trifluoroacetic (TFA) derivatives of both benzophenones (ACB-TFA and ACDB-TFA) can be chromatographed on OV-17, in a short time, with good electron-capture detector (ECD) responses. The mass spectra of these derivatives provide abundant molecular ions suitable for mass spectrometric detection by multiple ion detection (MID),  with a considerable improvement in specificity compared with the ECD responses. The detection limits in blood specimens have been established at 5-10 ng/ml by ECD and 0.5-0.8 ng/ml by MID. The method has been applied to the study of blood levels attained after i.v. and oral doses in rats and in man.