手性衍生化-HPLC法测定达托霉素中8种手性氨基酸的D,L-构型  

D, L-Configuration determination of eight kinds of chiral amino acids in daptomycin by chiral derivatization and HPLC

作　　者：刘浩[1] 裘亚[1] 

机构地区：[1]上海市食品药品检验所,上海201203

出　　处：《中国抗生素杂志》2016年第1期45-49,69,共6页Chinese Journal of Antibiotics

基　　金：重大新药创制专项化学新药质量标准研究与评价技术平台(No.2011ZX09303-001)

摘　　要：目的应用柱前手性衍生化-HPLC技术测定达托霉素中8种手性氨基酸的D,L-构型。方法取达托霉素溶于6mol/L盐酸溶液,经110℃水解7h,中和,在碱性条件下与Nα-(5-氟-2,4-二硝基苯基)-L-丙胺酰胺(FDAA)经微波辅助进行衍生化反应,再用非手性HPLC系统分离测定。结果各种氨基酸衍生物、FDAA以及反应副产物之间均可得到有效分离,仿制药与原研药的8种手性氨基酸的D,L-构型完全相同,也均与文献报道一致。结论该方法可应用于达托霉素中8种手性氨基酸的D,L-构型的测定。Objective To establish a method used for D, L-configuration determination of eight kinds of chiral amino acids in daptomycin by pre-column chiral derivatization and HPLC. Methods Daptomycin was dissolved in 6mol/L hydrochloric acid solution, and then was hydrolyzed for 7h at 110℃. After neutralization, the sample was derivatized with N^α-（5-fluoro-2,4-dinitrophenyl）-L-alaninamide （FDAA） under alkaline conditions, with the assistance of microwave. Then an achiral HPLC method was used for determination of the derivatized products. Results Applying the novel method, the derivatized products of amino acids, FDAA and reaction by-product were well separated. The D, L-configuration of eight kinds of chiral amino acids in generic drug were identical with those in originator product, and also consistent with the literature report. Conclusion The present method was suitable for D, L-configuration determination of eight kinds of chiral amino acids in daptomycin.

关 键 词：D L-构型 手性氨基酸 达托霉素 手性衍生化 HPLC 

分 类 号：O657.7[理学—分析化学] R978.11[理学—化学]