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目的建立人血浆中米格列奈浓度的HPLC-MS/MS检测方法。方法采用HPLC-MS/MS法测定米格列奈的血药浓度。以那格列奈为内标,流动相A:0.2%甲酸水溶液(含5mmol·L~(-1)乙酸铵),流动相B:甲醇-乙腈=1∶1(含0.2%甲酸,5mmol·L~(-1)乙酸铵),流速为0.3ml·min-1,进样量为10μl。结果标准曲线方程分别为:R=6.89 C-0.0153(r=0.9964,权重为1/C2)。血浆中米格列奈的浓度在0.0105~2.10μg·ml~(-1)范围内与米格列奈峰面积/内标峰面积具有良好的线性关系。血浆样品中米格列奈的平均萃取回收率为(96.47±6.18)%(n=15);内标的平均萃取回收率为(95.43±3.93)%(n=15)。血浆样品中米格列奈低、中、高3个浓度的日内RSD分别为3.14%~7.28%、3.50%~5.70%、4.41%~12.68%,日间RSD分别为5.64%、7.31%、10.37%。各项稳定性试验表明该方法符合要求。结论本试验所建立的米格列奈HPLC-MS/MS测定法能专属、灵敏、准确的测定其血药浓度,可应用于米格列奈在人体内的药动学特征研究。
Objective To establish a HPLC-MS / MS method for the determination of mitiglinide in human plasma. Methods The plasma concentrations of mitiglinide were determined by HPLC-MS / MS. With nateglinide as internal standard, the mobile phase A consisted of 0.2% formic acid aqueous solution (containing 5 mmol·L -1 ammonium acetate), mobile phase B: methanol-acetonitrile = 1: 1 L -1 ammonium acetate) at a flow rate of 0.3 ml · min -1. The injection volume was 10 μl. Results The standard curve equations were: R = 6.89 C-0.0153 (r = 0.9964, weight 1 / C2). The concentration of mitiglinide in plasma ranged from 0.0105 to 2.10μg · ml ~ (-1) and had a good linear relationship with the area of mitiglinid peak / internal standard peak area. The average extraction recovery of mitiglinide in plasma sample was (96.47 ± 6.18)% (n = 15). The average internal standard extraction recovery was (95.43 ± 3.93)% (n = 15). The intra-day RSD of low, medium and high concentrations of mitoxanil in plasma samples ranged from 3.14% to 7.28%, 3.50% to 5.70% and 4.41% to 12.68%, respectively. The intraday RSD were 5.64%, 7.31% and 10.37 %. Various stability tests show that the method meets the requirements. CONCLUSION The established mitoxanil HPLC-MS / MS assay can be used to determine its plasma concentration exclusively, sensitively and accurately and can be applied to the study of the pharmacokinetics of mitiglinide in human.