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

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作  者:刘文荣 庄绪慧 孙合园 朱丽萌 康毅敏[2] 王帆[3] 王文艳[1] LIU Wen-rong;ZHUANG Xu-hui;SUN He-yuan;ZHU Li-meng;KANG Yi-min;WANG Fan;WANG Wen-yan(School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, China;Psychosomatic Medicine Research Division, Inner Mongolia Medical University, Huhhot 010110, China;Beijing Huilongguan Hospital, Peking University, Beijing 100096, China)

机构地区:[1]烟台大学新型制剂与生物技术药物研究山东省高校协同创新中心、分子药理和药物评价教育部重点实验室(烟台大学),山东烟台264005 [2]内蒙古医科大学精神医学研究室,呼和浩特010110 [3]北京大学北京回龙观医院,北京100096

出  处:《烟台大学学报:自然科学与工程版》2019年第1期31-37,共7页Journal of Yantai University(Natural Science and Engineering edirion)

基  金:北京市自然科学基金资助项目(7152074).

摘  要: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AgilentXDB-C18柱(150×2.1mm,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>0.9958),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.

关 键 词:非典型抗精神分裂药 单药治疗 多药治疗 LC-MS/MS 治疗药物浓度监测 

分 类 号:R917[医药卫生—药物分析学;医药卫生—药学]

 

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