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目的:建立超高效液相色谱串联质谱(UPLC-ESI-MS/MS)法测定大鼠血浆中埃索美拉唑的含量,并应用于药动学研究。方法:血浆样品经蛋白沉淀法处理后,采用Agilent ZORBAX Eclipse Plus C18色谱柱(50 mm×2.1 mm,1.8μm),以A(0.1%甲酸)-B(乙腈)(80∶20)为流动相,柱温为35℃,采用电喷雾电离源(ESI)源,以多反应监测(MRM)方式进行正离子检测。通道分别为m/z346→198(埃索美拉唑)和m/z254→156(内标,磺胺甲卟恶唑),用非室模型计算药动学参数。结果:埃索美拉唑的线性范围为0.2~20 ng·mL~(-1)(r=0.999 7),检出限为0.12 ng·mL~(-1),日内日间精密度均小于10%。低、中、高3个浓度提取回收率均大于90%,达峰时间(tmax)为(1.5±0.5)h,达峰浓度(Cmax)为(620.65±2.89)ng·mL~(-1),药物浓度-时间曲线下面积(AUC0-t)为(2 530.68±60.17)ng·h·mL~(-1),半衰期(t_(1/2))为(3.87±0.03)h。结论:该方法操作简便、快速、准确度高、重复性好,可用于大鼠血浆中埃索美拉唑的测定和药动学研究。
Objective: To establish a method for the determination of esomeprazole in rat plasma by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-ESI-MS / MS) and to study its pharmacokinetics. Methods: After the plasma samples were treated by protein precipitation method, the mobile phase was A (0.1% formic acid) -B (acetonitrile) (80:20) with Agilent ZORBAX Eclipse Plus C18 column (50 mm × 2.1 mm, The column temperature was 35 ℃. The positive ion was detected by MRM with electrospray ionization source (ESI). The channels were m / z 346 → 198 (esomeprazole) and m / z 254 → 156 (internal standard, sulfamethoxazole). Pharmacokinetic parameters were calculated using a non-compartmental model. Results: The linear range of esomeprazole was 0.2 ~ 20 ng · mL -1 (r = 0.999 7). The detection limit was 0.12 ng · mL -1. The intra-day and inter-day precision were less than 10%. The recovery rates of the three concentrations were higher than 90%, the peak time (tmax) was (1.5 ± 0.5) h, the peak concentration (cmax) was (620.65 ± 2.89) ng · mL -1 (AUC0-t) was (2 530.68 ± 60.17) ng · h · mL -1, and the half-life (t 1/2) was 3.87 ± 0.03 h in the drug concentration-time curve. Conclusion: The method is simple, rapid, accurate, reproducible and can be used for the determination of esomeprazole in rat plasma and pharmacokinetic study.