摘要
目的 建立鼠肝微粒体中盐酸普罗帕酮消旋体 (R/S PPF)的手性拆分法 ,以研究大鼠肝微粒体中R/S PPF体外代谢的立体选择性。方法 用GITC柱前手性衍生化、反相高效液相色谱法拆分R/S PPF ;外标法定量 ;体外微粒体孵育试验。结果 基线拆分了盐酸普罗帕酮两对映体 ,容量因子分别为 7 9和 9 5 ,分离系数α为 1 2 ,分离度R为 1 9,线性范围 0 5~ 32 0 μg·mL-1,检测限 10 0ng·mL-1,定量限 5 μg·mL-1(RSD <15 % )。平均绝对回收率S PPF为 77 1% ,R PPF为 76 0 %。平均日内、日间精密度均 <10 %。在DEX和BNF诱导鼠肝微粒体中 ,PPF的代谢呈显著的立体选择性 ,在空白对照微粒体中的代谢未呈立体选择性。结论 此法简便、经济 ,可用于鼠肝微粒体中R/S PPF代谢的立体选择性研究。
AIM To separate propafenone enantiomers in rat liver microsomal incubates and investigate probable stereoselectivity in their N dealkylation. METHODS The concentration of each enantiomer in rat liver microsomal incubates was determined through precolumn derivatization with 2,3,4,6 tetra O acetyl β glucopyranosyl isothiocyanate (GITC), followed by RP HPLC assay. RESULTS A baseline separation of propafenone enantiomers was achieved on C 18 ODS column, with methanol — water — glacial acetic acid (67∶33∶0 05) as mobile phase. The assay was linear from 0 5 to 320 μg·mL -1 for each enantiomer, and the limit of detection was 100 ng·mL -1 . The method affords the average recoveries of 77 1% for R propafenone and 76 0% for S propafenone. Stereoselectivity was observed for the phase I metabolism of racemic propafenone in dexamethasone, β naphthoflavone induced rat liver microsomal incubates,but not in controls. CONCLUSION The method is simple, cheap and can be applied to study the metabolism of R and S propafenone in vitro . Stereoselectivity exists in their N dealkylation.
出处
《药学学报》
CSCD
北大核心
2000年第5期370-373,共4页
Acta Pharmaceutica Sinica
基金
国家自然科学基金!( 3 9770 868)
关键词
盐酸普罗帕酮对映体
肝微粒体
手性拆分
R/S-RRE
propafenone
2
3
4
6 tetra
O
acetyl β glucopyranosyl isothiocyanate
stereoselectivity
RP HPLC