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目的:建立LC-MS/MS法同时测定血浆伊潘立酮(iloperidone,ILP)及其两个代谢产物羟基伊潘立酮(hydroxy iloperidone,P88)和伊潘立酮羧酸(iloperidone carboxylic acid,P95)的药浓度。方法:色谱柱为Agilent C8(100 mm×4.6 mm,3.5μm),流动相为乙腈-2 mmol·L-1醋酸铵水溶液(含1.5%甲酸)=28∶72,流速为600μL·min-1,采用ESI源正离子模式,多反应监测方式测定。ILP,P88,P95的监测离子对分别为:m/z 427.2→233.2,m/z 429.2→261.2,m/z 429.2→233.2,内标氘代伊潘立酮(iloperidone-D3,ILP-D3)的监测离子对为m/z 430.2→233.1。结果:血浆ILP,P88和P95浓度分别在0.01~15 ng·m L-1,0.01~15ng·m L-1和0.02~20 ng·m L-1范围内线性均良好,日间、日内精密度均在可接受范围内,提取回收率较高,均大于75%。结论:该方法准确、灵敏度高、重现性好,能够较好地应用于ILP及其两个代谢产物的人体药动学研究。
OBJECTIVE: To establish a simultaneous LC-MS / MS method for the determination of plasma levels of iloperidone (ILP) and its two metabolites, hydroxy iloperidone (P88) and iloperidone carboxylic acid P95) drug concentration. METHODS: The chromatographic column was Agilent C8 (100 mm × 4.6 mm, 3.5 μm). The mobile phase was acetonitrile-2 mmol·L-1 ammonium acetate aqueous solution (containing 1.5% formic acid) = 28:72 and the flow rate was 600 μL · min-1 , Using ESI source positive ion mode, multi-reaction monitoring method. The ion pairs monitored for ILP, P88 and P95 were: m / z 427.2 → 233.2, m / z 429.2 → 261.2, m / z 429.2 → 233.2, and the internal standard iloperidone-D3 (ILP- The monitored ion pair is m / z 430.2 → 233.1. Results: The concentrations of plasma ILP, P88 and P95 were linear in the range of 0.01-15 ng · m L-1, 0.01-5 ng · m L-1 and 0.02-20 ng · m L-1, respectively. The intra- and inter-day precision Degree are within the acceptable range, extraction recovery rate is higher, are greater than 75%. Conclusion: The method is accurate, sensitive and reproducible. It can be applied to the study of human pharmacokinetics of ILP and its two metabolites.