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目的:建立一种灵敏、快速、稳定的液相色谱-串联质谱(UPLC-MS/MS)法用于测定人血浆中亚胺培南(IMP)的浓度,并用于研究接受连续性肾脏替代治疗(CRRT)的患者体内IMP的药代动力学。方法:血浆样品经乙腈沉淀蛋白后使用UPLC-MS/MS法分析。色谱柱为Phenomenex Kinetex~?HILIC(100mm×2.1 mm,2.6μm),流动相为0.1%甲酸、8 mmol·L~(-1)乙酸铵溶液-0.1%甲酸乙腈溶液,梯度洗脱,流速为0.3 m L·min~(-1),柱温为40℃,进样器温度为4℃。质谱采用电喷雾离子源(ESI),扫描方式为正离子模式,多重反应选择离子监测(MRM)扫描,IMP定量离子对为m/z 300.0→m/z 142.0,内标(美罗培南)为m/z 384.1→m/z 141.1。结果:IMP浓度在0.1~80μg·m L~(-1)范围内线性良好(r>0.99)。方法的日内、日间精密度的RSD均小于6.1%,准确度在104.4%~115.3%之间,基质效应在111.0%~111.7%之间,回收率在86.3%~92.0%之间。IMP在CRRT患者体内的半衰期t_(1/2)为(3.56±1.29)h,药时曲线下面积(AUC)为(45.47±2.67)mg·L~(-1)·h,表观分布容积(V)为(60.81±17.76)L,清除率(Cl)为(13.08±5.60)L·h~(-1),达峰浓度C_(max)为(14.98±8.68)μg·m L~(-1)。结论:本方法经验证,可用于测定人血浆中IMP的浓度。
OBJECTIVE: To establish a sensitive, rapid and stable liquid chromatography-tandem mass spectrometry (UPLC-MS / MS) method for the determination of imipenem (IMP) in human plasma and to study the effect of continuous renal replacement therapy (CRRT) in patients with IMP pharmacokinetics. Methods: Plasma samples were analyzed by UPLC-MS / MS after precipitation of proteins by acetonitrile. The chromatographic column was Phenomenex Kinetex ~? HILIC (100mm × 2.1 mm, 2.6μm). The mobile phase consisted of 0.1% formic acid and 8 mmol·L -1 ammonium acetate solution-0.1% formic acid in acetonitrile. 0.3 m L · min -1, the column temperature was 40 ℃, and the injector temperature was 4 ℃. Mass spectrometry was performed with electrospray ionization (ESI), positive ion scan mode and multiple reaction selective ion monitoring (MRM). The quantitative ion pair (m / z 300.0 → m / z 142.0) and internal standard / z 384.1 → m / z 141.1. Results: The concentration of IMP was linear in the range of 0.1 ~ 80μg · m L -1 (r> 0.99). The RSDs of intra-day and inter-day precision were less than 6.1%, the accuracy was between 104.4% and 115.3%, the matrix effects were between 111.0% and 111.7%, and the recovery rates were between 86.3% and 92.0%. The half-life (t 1/2) of IMP in patients with CRRT was (3.56 ± 1.29) h and the area under the curve (AUC) was (45.47 ± 2.67) mg · L -1 · h. The apparent volume of distribution (V) was (60.81 ± 17.76) L, the clearance rate (Cl) was (13.08 ± 5.60) L · h -1 and the peak concentration was (14.98 ± 8.68) μg · m L ~ -1). Conclusion: This method is validated and can be used to determine the concentration of IMP in human plasma.