Electron-capture gas chromatographic determination of loprazolam in plasma and a pharmacokinetic application

A sensitive and specific gas chromatographic method, using an electron capture detector, for the measurement of plasma concentrations of loprazolam (HR-158) is described. Retention times of the hydrolysis product of loprazolam (2-amino-2'-chloro-5-nitrobenzophenone) and of the internal standard (2-amino-2'-fluorobenzophenone) were, respectively, 9 and 7 minutes. The sensitivity of the assay was 1.0 ng ml-1 of plasma, and for drug concentrations ranging from 1.0 to 15 ng ml-1 the mean recovery from plasma was 94.4 per cent and the mean coefficient of variation 9.8 per cent. This method was used to determine some pharmacokinetic parameters of loprazolam after administration of 2 X 1 mg capsule doses to nine healthy, fasted volunteers. The mean t 1/2 was 6.4 h, mean AUC infinity 65.42 ng.h ml-1, and the mean clearance 0.51 l min-1.