Development of a HPLC-UV assay for silybin-phosphatidylcholine complex (silybinin capsules) and its pharmacokinetic study in healthy male Chinese volunteers

Abstract

To develop a new HPLC-UV method of determining silybin in human plasma and to study the pharmacokinetic of silybin-phosphatidylcholine complex (silybinin capsules) in healthy male Chinese volunteers using the new developed method. The assays were validated over the concentration range of 3.5-14336.0 ng·ml-1 in human plasma. In either matrix, the lower limit of quantitation was 3.5 ng·ml-1. The intra- and inter-day precision were less than 10% in terms of RSD. The absolute recoverys were more than 90%. The validated assay was suitable for pharmacokinetic studies of silybin. In order to assess its pharmacokinetic profile in human, plasma silybin levels were determined after administration of single oral doses of silybin-phosphatidylcholine complex (equivalent to 280mg silybin) to 20 subjects. Silybin was absorpted rapidly, the times to reach peak plasma concentration (Tmax) ranged from 0.67 to 2.67h, and the mean was 1.4h. Other Pharmacokinetic parameters of silybin in human were Cmax 4242.1±2252.9 ng·ml-1; AUC(0-∞) 5946.6±1898.9 ng·h·ml-1; Kel 0.31±0.08 h-1; t1/2 2.38±0.76 h; K a 5.48±2.00 h-1; CL 55.0±28.1 L·h-1; Vd 191.7±125.1 L, respectively.