LC-MS/MS法测定人血浆中4种非典型抗精神分裂药物及2种代谢物

LC-MS/MS Method for Determination of 4 Antipsychotics and 2 Metabolites in Human Plasma

建立了快速、灵敏、可靠的液相色谱串联质谱(LC-MS/MS)方法,用于同时测定治疗稳定期精神分裂患者血浆中4种非典型抗精神病药物利培酮、氯氮平、奥氮平、阿立哌唑和2种的代谢物9-羟基利培酮、脱氢阿立哌唑的浓度.血浆样品通过液-液萃取进行纯化并采用Agilent XDB-C18柱(150×2. 1 mm,3. 5μm)进行色谱分离. 6种分析物及其同位素内标均用正离子模式下的ESI源电离,并通过选择性反应监测进行测定. 6种分析物线性关系良好(r> 0. 995 8),批内批间精密度的变异系数小于13. 8%,准确度的偏差在±11. 7%以内.该方法已成功应用于抗精神分裂药物单药或多药治疗的稳定期精神分裂患者的治疗药物浓度监测.

A rapid, sensitive and reliable liquid chromatography tandem mass spectrometry (LC-MS/MS) method is established for the simultaneous quantification of four antipsychotics, including risperidone, clozapine, olanzapine, aripiprazole and metabolites 9-hydroxyrisperidone and dehydroaripiprazole in human plasma. Plasma samples are prepared by the liquid-liquid extraction. Chromatographic separation is performed on an Agilent XDB-C18 column (150×2.1 mm, 3.5 μm) with a gradient elution. 6 analytes and their isotope internal standards are ionized with an ESI source operated in positive ion mode and measured by selective reaction monitoring. The linearity is good ( r > 0.995 8). The intra-day and the inter-day precision of the method is less than 13.8%, and the accuracy is within ±11.7%. The LC-MS/MS method is successfully applied to the therapeutic drug monitoring study of the analytes in stable schizophrenia patients after adopting antipsychotic monotherapy or antipsychotic polypharmacy.