目的 建立人血浆格列美脲及其代谢物同时检测的超高液相色谱-质谱方法。方法 采用Waters 超高液相质谱仪,以Acquity UPLC BEH C₁₈柱(2.1 mm×50 mm,1.7 μm)为色谱柱;以乙腈-0.1%甲酸为流动相,流速为0.4 mLmin^-1,梯度洗脱;柱温为35 ℃。以格列本脲为内标,血浆经乙腈沉淀高速离心后检测。离子源为电喷雾离子源,正离子方式检测,扫描方式为多反应监测(MRM);用于定量分析的离子反应分别为:格列美脲 m/z 491.2→126.15,代谢物M1 m/z 507.3→126.1,内标 m/z 494.2→369.0。结果 血浆格列美脲浓度在2.5～400 μgL^-1内线性关系良好(r=0.999 8);低、中、高3个浓度(5、50、300 μgL^-1)的日内精密度RSD分别为7.23％、6.63％和4.69％,日间精密度RSD分别为8.66％、7.69％和5.76％;相对回收率分别为(102.57±5.43)％、(101.75±4.21)％和(101.67±3.81)％。代谢物M1浓度在0.5～100 μgL^-1内线性关系良好(r=0.999 5);低、中、高3个浓度(1、10、75 μgL^-1)的日内精密度RSD分别为8.74％、7.24％和4.33％,日间精密度RSD分别为10.68％、8.42％和5.64％;相对回收率分别为(103.12±6.52)％、(100.84±5.08)％和(99.01±3.22)％。结论 该方法简便、快速、准确,适用于血浆格列美脲及其代谢物的定量检测、药动学和药物相互作用研究。

OBJECTIVE To develop an ultra-high performance liquid chromatography-mass spectrometry method for the determination of glimepiride and its metabolites (M1) simultaneously in human plasma. METHODS The analytical column was packed with an Acquity UPLC BEH C₁₈. A mixture of acetonitrile-0.1% formic acid was used as the mobile phase with the flow rate at 0.4 mLmin^-1, gradient elution. The column temperature was set at 35 ℃. Glyburide was used as internal standard, plasma was precipitated by acetonitrile and glimepiride and its metabolites were detected after high-speed centrifugation.The mass spectrometric analysis was performed using an Acquity TQD triple quadrupole mass spectrometer coupled with an electro-spray ionization (ESI) source in the positive ion mode. The MRM transitions of m/z 491.2→126.15, m/z 507.3→126.1 and m/z 494.2→369.0 were used to quantify for glimepiride, M1 and internal standard, respectively. RESUTLS Excellent liner relationship of glimepiride was obtained from the range of 2.5 to 400 μgL^-1(r=0.999 8). The intra-day RSD were 7.23％, 6.63％and 4.69％ and inter-day RSD were 8.66％、7.69％ and 5.76％ respectively at three concentrations (5, 50, 300 μgL^-1), the relative recoveries were (102.57±5.43)％, (101.75±4.21)％ and (101.67±3.81)％ respectively. Excellent liner relationship of M1 was obtained from the range of 0.5 to 100 μgL^-1(r=0.999 5). The intra-day RSD were 8.74％, 7.24％and 4.33％ and inter-day RSD were 10.68％, 8.42％and 5.64％ respectively at three concentrations (1, 10, 75 μgL^-1), the relative recoveries were (103.12±6.52)％, (100.84±5.081)％ and (99.01±3.22)％ respectively. XONCLUSION The method is simple, rapid, accurate and suitable for the quantitative determination of plasma glimepiride and its metabolites, pharmacokinetic and drug interaction studies.