摘要
目的建立超高效液相串联质谱法快速测定大鼠体内格列美脲及其代谢物羟基格列美脲的浓度。方法用乙腈沉淀蛋白的方法处理血浆,色谱柱为ACQUITY UPLC HSS T3柱(50 mm×2.1 mm,1.8μm);流动相为乙腈-0.1%甲酸水,梯度洗脱;流速为0.4 m L·min-1;用正离子多离子反应监测(MRM)扫描,内标为甲苯磺丁脲。结果血浆中格列美脲和羟基格列美脲的线性范围为10~800μg·L-1和1~80μg·L-1(r=0.999 9和0.999 5),最低定量限为2.00μg·L-1和0.50μg·L-1,回收率均为94.05%~105.33%。两者的日内、日间精密度RSD均<8.20%。结论该方法操作简便、快捷,灵敏度高,适于大鼠体内格列美脲及其代谢物的药动学研究。
AIM To develop an ultra performance liquid chromatography-tandem mass spectrometry method for the determination of glimepiride and its metabolite( hydroxyglimepiride) in rat plasma. METHODS The plasma was precipitated with 200 μL acetonitrile. An ACQUITY UPLC HSS T3 column( 50 mm × 2. 1 mm,1. 8 μm)was used as the stationary phase. The mobile phase consisted of acetonitrile-0. 1% formic acid water with gradient elution,and the flow rate was 0. 4 m L·min-1. The analytes were detected with positive electrospray ionization in multiple reaction monitoring( MRM) mode and tolbutamide was used as internal standard. RESULTS Excellent linear calibration curves of glimepiride and hydroxyglimepiride were obtained in the concentration range of 10-800μg·L-1and 1-80 μg·L-1( r = 0. 999 9 and 0. 999 5). The lower limit of quantification was 2. 0 μg·L-1and0. 50 μg·L-1. The average recovery was 94. 05%-105. 33%. The intra-and inter-day relative standard deviations were all less than 8. 20%. CONCLUSION The method is simple,rapid and sensitive,which is suitable for pharmacokinetic study of glimepiride and its metabolite in rats.
出处
《中国临床药学杂志》
CAS
2015年第3期162-166,共5页
Chinese Journal of Clinical Pharmacy
基金
浙江省中西医结合学会临床药学科研基金(康恩贝麝香专项)(编号2013LYX014)
关键词
格列美脲
血药浓度
药动学
超高效液相串联质谱法
glimepiride
plasma concentration
pharmacokinetics
ultra performance liquid chroma-tography-tandem mass spectrometry
