SIMPLE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC SEPARATION OF OXAZEPAMAND ITS DIASTEREOISOMERIC GLUCURONIDES IN SERUM - APPLICATIONS IN A PHARMACOKINETIC STUDY IN SHEEP

This paper describes a highly specific and sensitive method for quanti fying oxazepam and its diastereoisomeric glucuronides in serum. The me thod involves sample clean-up by solid-phase extraction on C-18 cartri dge followed by quantitation on a reversed-phase HPLC column. Diazepam is used as internal standard. Extraction recovery from serum proved t o be more than 86%. Precision, expressed as C.V., was in the range 1.2 -9.5%. The limits of quantification were 40, 400, and 200 nmol/l for o xazepam, S-(+)- and R-(-)-glucuronides, respectively. This method was applied to the determination of oxazepam and its diastereoisomeric glu curonides in serum collected during a pharmacokinetic study performed in sheep after oral administration of racemic oxazepam. S-(+)/R-(-) ra tios were measured all along the sampling time collection and the phar macokinetic parameters were determined.