摘要
目的建立测定beagle犬内西罗莫司(SRL)血药浓度的UPLC-MS/MS联用方法。方法色谱柱为Agilent C18柱(50 mm×2.1 mm,1.7μm,);预柱为C18柱(4.0 mm×3.0 mm,5μm);流动相为乙腈-水(90∶10,v/v);流速为0.30 ml/min;柱温为50℃;进样室温度为4℃。离子源为ESI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m/z 936.6→m/z 409.7(西罗莫司)和m/z 826.6→m/z 415.4(内标他克莫司)。取全血样品经液-液萃取后进样20μl。结果 SRL在0.50～12.00 ng/ml浓度范围内呈良好的线性(r=0.999 7),定量下限0.5 ng/ml,日内、日间精密度(RSD)均小于15%,方法回收率均大于90%,萃取回收率大于76%。结论本方法具有样品处理简单,方法灵敏、快速、选择性强,满足西罗莫司在beagle犬体内药物检测的要求。
Objective To develop a UPLC-MS/MS method for the determination of sirolimus in whole blood of beagle dog.Methods Sirolimus and internal standard Tacrolimus were extracted from whole blood with liquid-liquid extraction,then separated on a Agilent C18 column （50 mm × 2.1 mm, 1.7 μ
m） at the flow-rate of 0.30 ml/min. The mobile phase was Acetonitrile-water （90： 10） and the column temperature was 50℃. Electrospray ionization （ESI） source was applied and operated in the positive ion mode. Multiple reaction monitoring （ MRM ） mode with the transitions of m/z 936.6→409.7 and m/z 826.6→415.4 were used to quantify sirolimus and the internal standard,respectively. Results The calibration linea range of blood-Sirolimu concentrations was 0.50 - 12.00 ng/ml（ r = 0. 999 7）. The low limit of quantification was 0.50 ng/ml . The intra-and inter-day precisions （RSDs） were less than 15 %. The method recoveries were more than 90% . The extraction recoveries were more than 76%. Conclusions The method was specific, sensitive,rapid and suitable for the pharmacokinetic study of sirolimus in whole blood of beagle dog.
出处
《药学实践杂志》
CAS
2011年第5期353-355,375,共4页
Journal of Pharmaceutical Practice
