液相色谱-串联质谱法测定人血浆中米格列奈浓度及其药动学研究

目的建立一种快速分析测定人血浆中米格列奈的液相色谱-串联质谱色谱法,用以研究米格列奈在健康人体内的药动学。方法以那格列胺为内标,血浆酸化后经液液萃取后,采用液相色谱-串联质谱法以多反应检测方式进行测定,选择监测的离子为m/z 316.2→298.2(米格列奈)和m/z 318.2→120.2 (那格列胺)。流动相以甲醇-10 mmol·L~(-1)醋酸铵水溶液(75:25,V/V),流速0.3 mL·min~(-1),色谱柱为Agilent Zorbax Eclipse Plus C_(18)(1.8μm,3 mm×150 mm);柱温:30℃。结果米格列奈在0.502 0～4 016μg·L~(-1)浓度范围内呈良好的线性关系(r=0.995),最低检测浓度为0.502 0μg·L~(-1),精密度和准确度试验均符合生物分析要求,应用此法测得5、10、20 mg剂量组不同给药方式、多个时间点的米格列奈血药浓度,结果呈线性动力学特征。结论该方法灵敏度高、专属性强、准确、简便,适用于米格列奈的人体药动学研究。

Determination of mitiglinide in human plasma by LC-MS/MS and study of pharmacokinetics

AIM To determine the concentration of mitiglinide in human plasma by LC-MS/MS and to study its pharmacokinetics.METHODS Acidified plasma samples were prepared by a simple liquid-liquid extraction with ethyl acetate.The chromatographic separation was performed on an Agilent Zorbax Eclipse Plus C_(18) column with a mobile phase of methanol -10 mmol·L~(-1) ammonium acetate solution.Analytes were detected with an Agilent 6410 Triple qudrupole mass spectrometer equipped with an electrospray ionization source in positive multiple reaction monitoringmode:m/z 316.2 (precursor ion) to 298.2 (product ion) for mitiglinide and m/z 318.2 (precursor ion) to 120.2(product ion) for the internal standard.RESULTS The standard curve was linear (r=0.995) over the concentration range of 0.502 0-4 016μg·L~(-1).Accuracy and precision were all within±15%.The lower limit of quantification for mitiglinide was 0.502 0μg·L~(-1).The linear pharma- cokinetics was detected in plasma concentrations of the single oral dose of 5 mg,10 mg and 20 mg group in these healthy volunteers.CONCLUSION A rapid,sensitive and simple LC-MS/MS method for determination of mitiglinide was development,and the assay was successful applied to a clinical pharmacokinetic study.