Selektive und sensitive Bestimmung von Nicergolin und Metaboliten in biologischen Medien durch HPLC zur Erforschung seines humanpharmakologischen Verhaltens / Selective and Sensitive Quantification of Nicergoline and Metabolites in Biologie Fluids by HPLC and its Application to Pharmacokinetic Research in Human

Abstract

A high performance liquid chromatographic method was developed to study the pharmacokinetics of nicergoline and its two main m etabolites in humans. The analytes are extracted from blood, plasma and urine into a mixture of chloroform and ether, which is optimised in terms of recovery and absence of interferences. The analytes are separated on a small bore column filled with octadecylsilica. the mobile phase was a ternary mixture of water, acetonitrile and tetrahydrofurane with diisopropylamine for pH adjustment. To maintain the chromatographic stability. the mobile phase is circulated and a saturator column inserted between pump and sampler. Nicergoline is very unstable in blood, it could not be determined in human body fluids after a single dose of 10 mg nicergoline. Metabolite 1 reaches plasma concentrations of about 2 ng/ml after 40 min. metabolite 2 gains to about 8 ng/ml after 4 h. 67% of the dosed nicergoline are excreted in urine as free metabolite 2. free metabolite 1 occurred only in trace concentrations. 18.5% of the dosed drug were excreted as conjugated metabolite 2. 1.1% as conjugated metabolite 1.