沙美特罗和α-羟基沙美特罗的快速手性高效液相色谱测定法。应用于体外代谢研究。

Rapid chiral high-performance liquid chromatographic assay for salmeterol and alpha-hydroxysalmeterol. Application to in vitro metabolism studies.

作者信息

Zhang M, Fawcett J P, Shaw J P

机构信息

School of Pharmacy, University of Otago, Dunedin, New Zealand.

出版信息

J Chromatogr B Biomed Sci Appl. 1999 Jun 11;729(1-2):225-30. doi: 10.1016/s0378-4347(99)00156-5.

DOI:10.1016/s0378-4347(99)00156-5

PMID:10410946

Abstract

A rapid and sensitive chiral high-performance liquid chromatographic (HPLC) assay for the simultaneous determination of salmeterol and its principal human metabolite alpha-hydroxysalmeterol is described. The two pairs of enantiomers were resolved on a chiral-cellobiohydrolase column and detected by electrochemical detection at +700 mV. Standard curves were linear over the concentration range 0.1 to 4.0 microM for alpha-hydroxysalmeterol enantiomers and 2.5 to 40.0 microM for salmeterol enantiomers. Intra- and inter-day coefficients of variation were < 10%. The method was applied to a study of human hepatic metabolism in vitro which showed that microsomal metabolism of salmeterol to alpha-hydroxysalmeterol is not stereoselective.

摘要

描述了一种快速灵敏的手性高效液相色谱（HPLC）测定法，用于同时测定沙美特罗及其主要人体代谢物α-羟基沙美特罗。两对对映体在手性纤维二糖水解酶柱上得以分离，并通过在+700 mV下的电化学检测进行检测。α-羟基沙美特罗对映体的标准曲线在0.1至4.0 microM浓度范围内呈线性，沙美特罗对映体的标准曲线在2.5至40.0 microM浓度范围内呈线性。日内和日间变异系数均<10%。该方法应用于体外人体肝脏代谢研究，结果表明沙美特罗向α-羟基沙美特罗的微粒体代谢没有立体选择性。