Analysis of chiral non-steroidal anti-inflammatory drugs flurbiprofen,ketoprofen and etodolac binding with HSA  

作　　者：Chang-Chuan Guo Yi-Hong Tang Hai-Hong Hu Lu-Shan Yu Hui-Di Jiang Su Zeng 

机构地区：[1]Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University Hangzhou 310058, China [2]Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

出　　处：《Journal of Pharmaceutical Analysis》2011年第3期184-190,共7页药物分析学报（英文版）

基　　金：supported by National Major Projects for Science and Technology Development of Ministry Science and Technology of China (2009ZX09304-003)

摘　　要：The protein binding of non-steroidal anti-inflammatory drugs flurbiprofen, ketoprofen and etodolac with human serum albumin （HSA） was investigated using indirect chiral high performance liquid chromatography （HPLC） and ultrafiltration techniques. S-（-）-1-（1-naphthyl）- ethylamine （S-NEA） was utilized as chiral derivatization reagent and pre-column derivatization RP-HPLC method was established for the separation and assay of the three pairs of enantiomer. The method had good linear relationship over the investigated concentration range without interference. The average extraction efficiency was higher than 85% in different systems, and the intra-day and inter-day precisions were less than 15%. In serum albumin, the protein binding of etodolac enantiomers showed significant stereoselectivity that the affinity of S-enantiomer was stronger than R-enantiomer, and the stereoselectivity ratio reached 6.06; Flurbiprofen had only weak stereoselectivity in HSA, and ketoprofen had no stereoselectivity at all. Scatchard curves showed that all the three chiral drugs had two types of binding sites in HSA.The protein binding of non-steroidal anti-inflammatory drugs flurbiprofen, ketoprofen and etodolac with human serum albumin （HSA） was investigated using indirect chiral high performance liquid chromatography （HPLC） and ultrafiltration techniques. S-（-）-1-（1-naphthyl）- ethylamine （S-NEA） was utilized as chiral derivatization reagent and pre-column derivatization RP-HPLC method was established for the separation and assay of the three pairs of enantiomer. The method had good linear relationship over the investigated concentration range without interference. The average extraction efficiency was higher than 85% in different systems, and the intra-day and inter-day precisions were less than 15%. In serum albumin, the protein binding of etodolac enantiomers showed significant stereoselectivity that the affinity of S-enantiomer was stronger than R-enantiomer, and the stereoselectivity ratio reached 6.06; Flurbiprofen had only weak stereoselectivity in HSA, and ketoprofen had no stereoselectivity at all. Scatchard curves showed that all the three chiral drugs had two types of binding sites in HSA.

关 键 词：Protein binding Non-steroidalanti-inflammatorydrugs ENANTIOMER STEREOSELECTIVITY Human serum albumin 

分 类 号：O652.3[理学—分析化学] TQ460.6[理学—化学]