HPLCESIMS测定米格列奈钙的血药浓度及其药动学研究.docVIP

HPLC-ESI-MS测定米格列奈钙的血药浓度及其药动学研究 彭文兴1※ 程钢1 蔡立婧2 朱荣华1 （1中南大学湘雅二医院临床药学研究室 长沙 410011；2 中南大学药学院 长沙 410013） 摘要：目的：建立人血浆中米格列奈钙片HPLC-MS测定法，研究米格列奈钙片在健康志愿者的药物动力学。方法： 以那格列奈为内标，血浆样品过Strata-X固相萃取柱，用60 ％的乙腈洗脱，洗脱液20 uL注入Thermo C18色谱柱，柱温40 ℃。流动相组成为乙腈：0.1 ％甲酸溶液(60：40，V/V)，流速：1 mL/min，1/4分流进入色谱柱,质谱采用电喷雾电离源正源（ESI+），定量分析采用选择性离子监测（SIR）。30名健康志愿者（男女各半）随机分为三组，每组10人，分别单剂量口服米格列奈钙片5 mg（低剂量组）、10 mg（中剂量组）、20 mg（高剂量组），采集给药前和给药后血样,于-70 ℃冰箱总保存直到测定。结果：米格列奈在10-6054 ng/mL内线性关系良好，R=0.9982,萃取回收率均大于88 ％，方法回收率100.95 ％～103.88 ％，日内、日间RSD小于11 ％。口服三种剂量所得MRT、t1/2、Tmax相近，且与给药剂量无关。其体内吸收程度（Cmax、AUC0-8 ）与给药剂量有较好的线性关系，单剂量口服米格列奈后血药浓度时间曲线符合一级吸收代谢动力学。结论：HPLC-MS方法简单，准确度高，可用于米格列奈钙片在人体内的药物动力学研究。单剂量口服米格列奈后血药浓度时间曲线符合一级吸收代谢动力学。 关键词：米格列奈钙；HPLC-ESI-MS；药物动力学 ※：通讯作者：彭文兴，男，副教授。主要研究方向：药物动力学与药物相互作用。 High-performance liquid chromatography-electrospray ionization mass spectrometry determination of mitiglinide in human plasma and its pharmacokinetics Peng Wen-xing 1※， Cheng Gang1, CaiLi-jing2, Zhu Rong-hua 1 （1 Clinical Pharmaceutical Research Institute, Second Xiangya Hospital, Central South University, Changsha Hunan 410011, China ; 2 School of Pharmaceutical Sciences, Central South University, Changsha Hunan 410011, China; 2） ABSTRACT: OBJECTIVE: To establish a high performance liquid chromatographic coupled with electrospray ionization mass spectrometry (HPLC- MS/ESI) method for the determination of Mitiglinide in human plasma; and apply to pharmacokinetic study. METHOD: Nateglinide was used as internal standard. The plasma samples were extracted by Strata-X solid-phase extraction. 60 ％ acetonitrile eluting. The fractions were injected into evaporated Thermo C18 column(250mm×4.6mm，5 μm), with the column temperature was set at 40 ℃. The mobile phase was composed of acetonitrile and 0.1 % formic acid (60:40, v/v), with flow rate at 1.0mL/min. Split ratio was 1∶4.The compound was ionized in the turbo electrospray ionization (ESI) ion source of the mass spectrometer and was detected in the selected ion recording (SIR) m