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目的建立人血浆中米格列奈钙片UPLC-MS/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 24名健康志愿者(男女各半)随机分为3组,每组8人,分别单次口服米格列奈钙片5、10、20 mg,采集给药前和给药后不同时间的血样,于-70℃冰箱保存直到测定。血浆样品采用乙腈沉淀蛋白处理,以那格列奈为内标,色谱柱为ACQUITY UPLC BEH C18(50 mm×2.1 mm,1.7μm),柱温40℃。流动相:乙腈-0.1%甲酸溶液(58∶42,v/v),流速:0.25 mL.min-1,采用电喷雾电离源正源(ESI+),定量分析采用多重反应选择离子监测(MRM)。结果米格列奈在10.0~7 000.0 ng.mL-1线性关系良好,R2=0.999 8,萃取回收率88.89%~111.0%,方法回收率92.9%~100.5%,日内、日间RSD<12.3%。口服3种剂量所得MRT、t1/2、tmax相近,且与给药剂量无关。其体内吸收(Cmax、AUC0-8)与给药剂量有较好的线性关系。结论 UPLC-MS/MS方法简单,快速准确,单次口服米格列奈钙片后体内吸收程度与剂量间有线性关系。
Objective To establish a method for the determination of mitochondrial calcium in human plasma by UPLC-MS / MS and to study the pharmacokinetics of miglitzol in healthy volunteers. Methods Twenty-four healthy volunteers (half male and half female) were randomly divided into three groups with 8 in each. Oral administration of meglitinide 5, 10 and 20 mg, respectively, before and after administration Blood samples were stored at -70 ° C until assayed. Plasma samples were treated with acetonitrile-precipitated protein, with nateglinide as the internal standard. The column was ACQUITY UPLC BEH C18 (50 mm × 2.1 mm, 1.7 μm) with a column temperature of 40 ° C. The mobile phase was acetonitrile-0.1% formic acid solution (58:42, v / v), the flow rate was 0.25 mL.min-1, electrospray ionization source (ESI +) was used and the quantitative analysis was performed with multiple reaction selective ion monitoring . Results The results showed that the linear relationship of mitoxantrone between 10.0 and 7 000.0 ng.mL-1 was good, R2 = 0.999 8, the extraction recovery was 88.89% ~ 111.0%, and the recovery was 92.9% ~ 100.5%. The intra- and interday RSD was less than 12.3% . The results of oral administration of three doses of MRT, t1 / 2, tmax similar, and the dose has nothing to do. The body absorption (Cmax, AUC0-8) and the dose has a good linear relationship. Conclusion The UPLC-MS / MS method is simple, rapid and accurate. The linear relationship between the absorption and the dose of mitochondrial calcium after a single oral administration of UPLC-MS / MS.