Achiral and chiral determination of ciprofibrate and its glucuronide in human urine by capillary electrophoresis.

A method for achiral separation of the racemic hypolipidaemic agent ciprofibrate and its main metabolite ciprofibrate glucuronide by capillary electrophoresis (CE) was developed. The glucuronide was isolated from urine by chromatographic procedures and characterized by alkaline as well as enzymatic hydrolysis and mass spectrometric and nuclear magnetic resonance experiments. Chiral discrimination of the ciprofibrate enantiomers and their diastereomeric glucuronides by CE was achieved by the use of gamma-cyclodextrin as buffer additive. The fractionated crystallization of ciprofibrate yielded the R-(+)-enantiomer as less soluble diastereomeric salt with (+)-1-phenylethylamine. This allowed the identification of the enantiomers of ciprofibrate as well as the diastereomeric glucuronides of ciprofibrate by CE. In a study with three volunteers inter- and intra-individual differences of ratios of both ciprofibrate glucuronides in urine were observed. After oral administration of a single dose of the racemate the S-ciprofibrate glucuronide was mainly excreted in the first time intervals, in the last time intervals the R-glucuronide dominated.