液相色谱串联质谱法检测10种精神药物的实验室间比对  

Interlaboratory comparison of 10 psychotropic drugs detected by liquid chromatography-tandem mass spectrometry

作　　者：贺静[1,2] 齐小梅[1,2] 郭桂欣 周春燕[1] 李文标 He Jing;Qi Xiaomei;Guo Guixin;Zhou Chunyan;Li Wenbiao(Department of Clinical Laboratory,Beijing Key Laboratory of Mental Disorders,National Clinical Research Center for Mental Disorders&National Center for Mental Disorders,Beijing Anding Hospital,Capital Medical University,Beijing 100088,China;Advanced Innovation Center for Human Brain Protection,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学附属北京安定医院检验科,国家精神疾病医学中心,国家精神心理疾病临床医学研究中心,精神疾病诊断与治疗北京市重点实验室,北京100088 [2]人脑保护高精尖创新中心,首都医科大学,北京100069

出　　处：《实用药物与临床》2024年第7期498-505,共8页Practical Pharmacy and Clinical Remedies

基　　金：首都临床特色应用研究与成果推广项目(Z171100001017075)。

摘　　要：目的通过实验室间比对,了解液相色谱串联质谱法检测10种精神药物(氯氮平、奥氮平、利培酮、喹硫平、阿立哌唑、舍曲林、艾司西酞普兰、文拉法辛、度洛西汀、丙戊酸)及5种代谢物(去甲氯氮平、9-羟利培酮、N-脱烷基喹硫平、脱氢阿立哌唑、O-去甲文拉法辛)血清浓度的技术能力、质量管理现状及存在的问题,推进治疗药物监测工作的健康发展。方法选择8家已使用液相色谱串联质谱法开展了精神药物治疗药物监测的实验室,进行问卷调查,并进行质控血清及患者血清检测的实验室间比对试验。结果8家实验室使用的液相色谱串联质谱仪包括Waters、AB SCIEX、Agilent、岛津、德米特等,检测方法均为实验室自建,采用的样本前处理方法包括蛋白沉淀法和液液萃取法,液相和质谱等相关参数存在差异,方法学确证的批内和批间精密度均小于11%。8家实验室均开展了检测项目的室内质控,参加了室间质量评价活动。除去甲氯氮平外,其他被分析物质的质控血清检测结果的实验室间变异系数(CV)均小于25%。除去甲氯氮平低浓度水平、舍曲林低浓度水平外,其他被分析物质的质控血清检测结果的稳健变异系数(RCV)均小于15%。除去甲氯氮平、脱氢阿立哌唑外,在临床样本的检测范围内,各药物或代谢物超90%患者血清样品检测结果的实验室间CV小于15%。脱氢阿立哌唑患者血清样品检测结果的实验室间CV偏大,但也小于25%。对于去甲氯氮平,实验室E无论检测的质控血清还是患者血清,均存在大于50%的系统误差,剔除该实验室检测结果后,去甲氯氮平在其他实验室间检测结果的CV小于25%。结论液相色谱串联质谱法检测本研究所涉及药物或代谢物血清浓度的实验室间一致性尚可,检测结果具有可比性。部分实验室在标准曲线范围的设定、允许总误差的设定及应用、量值溯源等方面存�Objective To understand the technical ability,quality management status,and existing problems of liquid chromatography-tandem mass spectrometry in detecting serum concentrations of 10 psychotropic drugs(clozapine,olanzapine,risperidone,quetiapine,aripiprazole,sertraline,escitalopram,venlafaxine,duloxetine,valproic acid)and 5 metabolites(norclozapine,9-hydroxyrisperidone,N-dealkylated quetiapine,dehydroaliprazole,Odemethylvenlafaxine)by conducting interlaboratory comparisons,and promote the healthy development of therapeutic drug monitoring.Methods Eight laboratories that carry out psychotropic drug TDM by liquid chromatographytandem mass spectrometry were selected for comparison among the laboratories in quality control serum and patient serum,and a questionnaire survey was conducted.Results Liquid chromatography-tandem mass spectrometers used by the eight laboratories were brands such as Waters,AB SCIEX,Agilent,Shimadzu,and Demeter.The sample pretreatment methods they used were protein precipitation and liquid-liquid extraction.The parameters of liquid chromatograpyh and mass spectrometry were different.The within-run and between-run precision was less than 11%in method validation by all laboratories.Except for clozapine,the quality control serum interlaboratory CV of all analytes'concentration was less than 25%.Except for the low level of norclozapine and sertraline,the robust coefficient of variation(RCV)of all analytes was less than 15%.Except for clozapine and dehydroaliprazole,the inter-laboratory CV of analyte concentration with over 90%of drugs or metabolites was less than 15%.The inter-laboratory CV of dehydroaliprazole concentration was relatively large,but also less than 25%.Laboratory E had a systematic error of more than 50%in both the quality control serum and patient serum tested for norclozapine.After excluding the results of laboratory E,the inter-laboratory CV of norclozapine was less than 25%.Conclusion The current liquid chromatography-tandem mass spectrometry methods developed by laboratories

关 键 词：精神药物 治疗药物监测 液相色谱串联质谱 实验室间比对 

分 类 号：R927.1[医药卫生—药学]