高效液相色谱法测定布洛芬的立体异构代谢物

High-performance liquid chromatographic determination of the stereoisomeric metabolites of ibuprofen.

作者信息

Rudy A C, Anliker K S, Hall S D

机构信息

Department of Medicine, Indiana University Medical School, Wishard Memorial Hospital, Indianapolis 46202.

出版信息

J Chromatogr. 1990 Jun 29;528(2):395-405. doi: 10.1016/s0378-4347(00)82397-x.

DOI:10.1016/s0378-4347(00)82397-x

PMID:2384577

Abstract

A stereospecific reversed-phase high-performance liquid chromatographic (HPLC) method has been developed to simultaneously quantitate the stereoisomers of the two major metabolites of ibuprofen: hydroxyibuprofen and carboxyibuprofen. The metabolites were derivatized with S-(alpha)-methylbenzylamine to form diastereomeric amides which were separated and quantified on a C8 column. The validity of the stereoselective assay was confirmed by comparison with a non-stereoselective HPLC method. The stereoselective assay was applied to the quantification of all the stereoisomeric ibuprofen metabolites in urine from human volunteers dosed with racemic ibuprofen or the individual enantiomers of ibuprofen. Significant substrate and product stereo-selectivities were observed in the formation of carboxyibuprofen.

摘要

已开发出一种立体专一性反相高效液相色谱（HPLC）方法，用于同时定量布洛芬的两种主要代谢物：羟基布洛芬和羧基布洛芬的立体异构体。代谢物用S-（α）-甲基苄胺衍生化，形成非对映体酰胺，然后在C8柱上进行分离和定量。通过与非立体选择性HPLC方法比较，证实了立体选择性测定的有效性。该立体选择性测定法应用于对服用消旋布洛芬或布洛芬单个对映体的人类志愿者尿液中所有立体异构的布洛芬代谢物进行定量。在羧基布洛芬的形成过程中观察到了显著的底物和产物立体选择性。