Format

Send to

Choose Destination
J Pharm Biomed Anal. 2004 Mar 10;34(5):1071-8.

Stereoselective metabolism of silybin diastereoisomers in the glucuronidation process.

Author information

1
School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.

Abstract

A separation method for the hepatoprotective drug silybin and its metabolites by RP-HPLC was described. Based on this separation, the stereoselectivity of the metabolism of silybin was investigated by incubation of the drug and its two diastereoisomers with bovine liver microsomes. Information about the structures of these metabolites was obtained, using UV, HPLC/MS and NMR spectra. Four major metabolites (M(1), M(4) of silybin A and M(2), M(5) of silybin B), were prepared by preparative HPLC, and their configurations were accomplished by NMR spectra. A HPLC method was used to quantify the metabolites. The results showed that silybin was extensively metabolized and the major sites for glucuronidation were the C-20, C-7, at phenolic OH groups. Furthermore, the results obtained reveal that there was significant stereoselectivity in the glucuronidation process of silybin. Silybin B was glucuronidated at a more efficient rate than its diastereoisomer, and glucuronidation of silybin B was much preferred at the 20 position, while that of silybin A was similar at both 7 and 20 position.

PMID:
15019041
DOI:
10.1016/j.jpba.2003.12.002
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center