降血脂候选新药SIPI-4884有关物质的HPLC法测定

Determination of the Related Substances of A Hypolipidemic Candidate SIPI-4884 by HPLC

SIPI-4884是由本室自主研发的降血脂候选新药。本研究以其合成路线中的各中间体及可能的副产物或降解产物为对象,建立了高效液相色谱法检测有关物质。采用C18色谱柱,以四氢呋喃-甲醇-0.02 mol/L乙酸铵缓冲液(用乙酸调至pH 4.5)(13︰48︰39)为流动相,检测波长255 nm,以检测非手性有关物质。SIPI-4884对映异构体的色谱条件为:CHIRALCEL AS-H色谱柱,流动相为正己烷-乙醇-三氟乙酸(80︰20︰0.1),检测波长255 nm。3批样品的总杂质量都小于1%,其中最大杂质是5-羰基物。

SIPI-4884 is a hypolipidemic candidate developed by our lab. The HPLC methods were established for determination of its related substances with the intermediates and possible by-products in the synthesis as the references. For the achiral impurities, a C18 column was used with the mobile phase of tetrahydrofuran-methanol-0.02 mol/L ammonium acetate buffer （adjusted to pH 4.5 with acetic acid） （13 ： 48 ： 39） at the detection wavelength of 255 nm. A CHIRALCEL AS-H column was used with the mobile phase of hexane-ethanol-TFA （80 ： 20 ： 0.1） for the determination of the enantiomer in SIPI-4884. The determination on three batches of SIPI-4884 samples showed that the content of total related substances was less than 1% and the greatest one was the 5-oxo-compound.