西沙必利在新型键合手性柱上的拆分及其在血浆中的含量测定

Separation and Quantitative Determination of Cisapride Enantiomers on a New Cellulose Bonded Chiral Stationary Phase

建立一种用新型键合纤维素手性固定相拆分西沙必利对映体的高效液相色谱方法,并利用此方法测定血浆中西沙必利的含量.使用Chiralpak IC色谱柱（250 mm×4.6 mm,5μm）,流动相为正己烷-异丙醇-二乙胺（体积比80∶ 20∶0.1）,流速0.8 mL/min,检测波长273 nm,柱温25℃.取血浆200 μL,加入西沙必利标准溶液10 μL,碱化后用正庚烷-异戊醇（体积比95∶5）提取,40℃氮气吹干.结果表明：西沙必利对映体在新型键合直链纤维素衍生化合物手性固定相上能够完全分离,分离度为1.65;其血浆提取回收率达87％,线性范围为10～ 160 μg/mL,最低检测限为5 μg/mL,RSD＜4.0％.本方法可方便地实现西沙必利对映体的分离及其在血浆中的含量测定,为临床上西沙必利的血药浓度监测及药代动力学研究提供了便捷、灵敏的分析手段.

A liquid chromatographic method for the chiral separating enantiomers of cisapride in plasma was developed.Cisapride enantiomers were separated and determinated by a Chiralpak IC chiral column （250 mm ×4.6 mm,5 μm） at 25 ℃ and detected at 273 nm,the mobile phase used was n-hexane-isopropanol （80∶ 20,0.1％ DEA） at a flow rate of 0.8 mL/min.Alkalinized samples of plasma （200 μL） were extracted with n-heptane-isopentanol （95∶ 5）.The organic phase was evaporated to dryness under nitrogen at 40 ℃.The results showed that cisapride enantiomers were separated on a new cellulose bonded chiral stationary phase and the resolution was 1.65.The mean extraction efficiency was 87％.Calibration plots in rat plasma were linear from 10 to 160 μg/mL.The limit of detection was 5 μg/mL and RSD ＜4.0％.The present method could be easily used for separating the enantiomers of cisapride and determination of cisapride enantiomers in plasma.It provided a new approach for the determination of plasma concentration and its pharmacokinetic studies.