Chiba K, Horii H, Chiba T, Kato Y, Hirano T, Ishizaki T
Department of Clinical Pharmacology, International Medical Center of Japan, Tokyo.
J Chromatogr B Biomed Appl. 1995 Jun 9;668(1):77-84. doi: 10.1016/0378-4347(95)00050-s.
A simple high-performance liquid chromatographic method for the measurement of diazepam (DZP) and its major metabolites, N-desmethyldiazepam (DMDZP), temazepam (TZP) and oxazepam (OZP) in urine was developed. Preliminary studies of DZP metabolism were also undertaken in four healthy volunteers after administration of a single oral dose (4 mg) of DZP. The assay allowed the simultaneous determination of all analytes in 1 ml of urine and the detection limit was 2 ng/ml with a signal-to-noise ratio of 3. None of 22 drugs and 17 metabolites, except for mianserin, maprotiline and imipramine N-oxide, interfered with the detection of DZP metabolites. Recoveries of the analytes and the internal standard (prazepam) were > 82%. Intra- and inter-assay coefficients of variation for all analytes were < 5.5 and 4.1%, respectively. The mean (+/- S.D.) cumulative urinary excretions of DMDZP, TZP and OZP over 96 h after a single oral administration of DZP were 3.9 +/- 0.4, 6.6 +/- 1.4 and 2.8 +/- 0.6% of the dose, respectively. The urinary excretion of DZP was under the detection limit.
