自建色谱法血药浓度监测靶值建立及与不同方法测定水平的比较——以硫唑嘌呤代谢物和卡马西平为例  

Establishment of target values in measurement of serum drug concentration monitoring by laboratory-developed liquid chromatography and comparison of immunoassay and chromatography for quantification:examples of azathioprine metabolites and carbamazepine

作　　者：宋帅 刘加涛[1,2] 孙小珊 苏涌 沈陈林[3] 汪生 夏泉 SONG Shuai;LIU Jia-tao;SUN Xiao-shan;SU Yong;SHEN Chen-lin;WANG Sheng;XIA Quan(Department of Pharmacy,First Affiliated Hospital,Anhui Medical University,Anhui Hefei 230022,China;GradeⅢPharmaceutical Chemistry Laboratory of State Administration of Traditional Chinese Medicine,Anhui Hefei 230022,China;School of Pharmacy,Anhui Medical University,Anhui Hefei 230032,China;Center for Scientific Research,Anhui Medical University,Anhui Hefei 230032,China)

机构地区：[1]安徽医科大学第一附属医院药剂科,安徽合肥230022 [2]国家中医药管理局中药化学三级实验室,安徽合肥230022 [3]安徽医科大学药学院,安徽合肥230032 [4]安徽医科大学科研实验中心,安徽合肥230032

出　　处：《中国医院药学杂志》2021年第18期1860-1865,共6页Chinese Journal of Hospital Pharmacy

基　　金：安徽省“十三五”临床重点专科建设项目(编号:卫科教秘[2017]529号)。

摘　　要：目的:探索自建色谱法血药浓度监测靶值的建立;对比色谱法和免疫法在血药浓度测定的水平差异。方法:选择安徽医科大学第一附属医院硫唑嘌呤代谢物和卡马西平血药浓度监测分别作为实验室自建色谱法和不同测定方法的项目代表。回顾性分析硫唑嘌呤代谢物部分质控数据,以即刻质控法初步建立室内靶值,Westgard多规则质控对该项目开展常规质控;43例卡马西平样本分别由实验室HPLC和全自动生化分析仪以及第三方医学实验室,通过相关和回归分析评价检验方法一致性。结果:硫唑嘌呤代谢物项目在第16次质控监测提示告警,第17次失控记录也证实其存在异常离群。常规检测过程中累积失控2次即2_(2s)及1_(3s)记录各1次。三水平质控品累积变异系数分别为8.85%、7.46%和4.73%。3组卡马西平血药浓度测定数据均为非正态分布,其中实验室免疫法测定质量浓度结果最高(中位数为6.00μg·mL^(-1)),第三方实验室测定结果次之(中位数为5.50μg·mL^(-1)),而实验室色谱法测定结果最小(中位数为3.80μg·mL^(-1))。第三方实验室与实验室免疫法、第三方实验室与实验室色谱法以及实验室色谱法与免疫法其3组方法比较的秩相关系数分别为0.984、0.975和0.956,Passing-Bablok回归方程分别为:y=0.298+0.817x,y=-0.246+1.539x,y=-1.009+1.947x。结果表明,以上测定方法的一致性较好。结论:即刻质控法可用于自建色谱法血药浓度监测的简易室内质控程序。色谱法和免疫法在卡马西平血药浓度测定中存在基线水平差异。OBJECTIVE To explore the process of establishing target value of serum drug concentration monitoring by laboratory-development liquid chromatography and examine immunoassay versus liquid chromatography methods for measuring serum drug levels.METHODS Therapeutic monitoring of azathioprine metabolites and carbamazepine were representatives of laboratory-developed liquid chromatography and different assays.Quality control data of azathioprine metabolites essay was analyzed for determining target value by instant technique.Westgard rules were followed for routine quality control.Forty-three serum samples were collected for quantitative determination of carbamazepine concentration by the independent clinical laboratory and HPLC & immunoassay routinely.RESULTS Out-of-control alarm occurred at the sixteenth test.The outliers were also proved by the seventeenth results.Control observations exceeding 2_(2s) and 1_(3s) were recolonized by Westgard rules and presented by Z-score chart.Cumulative coefficient of variations of three levels of QC materials was 8.85%,7.46% and 4.73%.Carbamazepine concentrations displayed a non-normal distribution and the immunoassay levels(median concentration 6.00 μg·mL^(-1))were significantly higher than those at an independent clinical laboratory(median 5.50 μg·mL^(-1))and HPLC(median 3.80 μg·mL^(-1)).Spearman’s correlation coefficient among an independent clinical laboratory and immunoassay & HPLC at our laboratory was 0.984,0.975 and 0.95 respectively.Passing-Bablok regression equations were as follows: y=0.298+0.817x,y=-0.246+1.539x and y=-1.009+1.947x.The results suggested that the agreement of these methods was quite acceptable.CONCLUSION Instant technique quality control may be used as a simple internal quality control of serum drug concentration monitoring by laboratory-development liquid chromatography.And there is a significant quantitative level difference between immunoassay and HPLC.

关 键 词：室内质控 即刻质控法 治疗药物监测 自建色谱法 

分 类 号：R197[医药卫生—卫生事业管理]