摘要:
目的 建立液质联用色谱法(LC-MS-MS)测定人血浆中非布司他(febuxostate)浓度。 方法 空白血浆加非布司他,用乙腈作为沉淀剂,取上清液用于LC-MS-MS分析。分析柱为Thermo Biobasic-8柱(5 μm,50 mm×2.1 mm),流动相为乙腈-10 mmol/L乙酸铵(含0.05% 甲酸)(70:30),流速为0.2 ml/min;质谱条件:电喷雾离子化电离源ESI负离子检测,喷雾电压(SP)3 500 kV,鞘气(SGP)流速10 Arb,辅助气(AGP)流速45 Arb,毛细管温度(TEM)270℃;非布司他和内标苯扎贝特的碰撞能量分别为10 eV、18 eV;选择反应监测(SRM)分别测定非布司他和内标苯扎贝特负离子m/z 315→271和m/z 360→274。 结果 非布司他在10~8 000 μg/L检测浓度范围内呈良好线性关系(r>0.99),最低定量限(LLOQ)为10 μg/L,绝对回收率在85%以上,高中低3种浓度的日内和日间RSD<15%。 结论 该方法操作简便、灵敏、准确,适用于临床非布司他的血药浓度监测及其药动学研究。
Abstract:
Objective To establish a LC-MS-MS method for determining febuxostate in human plasma. Methods Febuxostate added into blank plasma was sedimented by acetonitrile, and the supernatant was determined by LC-MS-MS. Analytical column was Thermo Biobasic-8, 5 μm, 50 mm×2.1 mm(ID). The mobile phase consisted of acetonitrile-10 mmol/L ammonium acetate (0.05% acid=70:30 at a flow rate of 0.2 ml/min. Mass spectrum conditions:ESI-was performed in the SRM mode using target ions m/z 315→271 (10 eV)(febuxostate), m/z 360→274 (18 eV)(bezafibrate), SP 3 500 kV, SGP 10 Arb, AGP45 Arb, TEM 270℃. Results The calibration curve was linear over the range of 10-8 000 μg/L. The LLOQ of Febuxostate in plasma was 10 μg/L.The extracted recovery was >85%.The intra-and inter-day RSD were <15%. Conclusion The method was sensitive, simple and accurate to determinate febuxostate plasma concentration and to study pharmacokinetics of febuxostate.
点击查看大图
下载:
