LC-MS/MS法测定人血浆中米格列奈浓度

Determination of Mitiglinide in Human Plasma by LC-MS/MS

建立高效液相色谱-质谱联用法测定人血浆中米格列奈浓度,选用Kromasil-C18色谱柱（50 mm×4.6mm×5μm）,以V（乙腈）∶V（0.1%甲酸）=75∶25的1 mmol.L^-1甲酸铵溶液为流动相,采用等度洗脱进行分离,样品用沉淀蛋白法处理后进样。选用3200QTrap型三重四极杆串联质谱仪的多重反应监测（MRM）扫描方式进行检测。米格列奈的线性范围为3.0-3 000.0μg.L^-1,定量下限为3.0μg.L^-1。准确度与精密度结果显示,方法日间、日内变异均小于15%,相对偏差-1.40%-2.07%,方法提取回收率为（98.2±7.6）%,稳定性较好。该方法快速、灵敏,专属性强、重现性好,可用于人体血浆中米格列奈浓度的测定和药代动力学研究。

Mitiglinide in human plasma was determined by LC-MS/MS. Mitiglinide and the internal standard were extracted from plasma by acetonitrile, which was used as deproteinated solvent, and then separated on a Kromasil-C18 column （50 mm×4.6 mm×5μm）. The mobile phase consisted of acetonitrile-1 mmol · L^-1 ammonium formate （containing 0. 1% formic acid） maintained at 30℃. The flow rate was 0.6 mL · min^-1 , and 20μL aliquot of residues were injected into the LC-MS/MS system. Detection was carried out by multiple reaction monitoring on an 3200Qtrap LC-MS/MS system. The assay is linear over the range 3.0-3 000.0μg· L^-1 with a lower limit of quantitation of 3.0μg· L^-1. Intra-day and inter-day precision are both less than 15 %, respectively. The relative deviation is in the range of -1.40%-2.07%. The recoveries of Mitiglinide are （98.2 4-7.6）%, and stabilities are good. It is a rapid, sensitive, selective and reliable method for the determination of Mitiglinide in human plasma. The assay can be applied for the determination of Mitiglinide in human plasma and the study on pharmacokinetics.