摘要
目的建立环孢素A和他克莫司治疗药物监测的高效液相色谱-串联质谱(HPLC-MS/MS)质控方法,应用Westgard多规则理论对质控样品进行评估。方法利用HPLC-MS/MS建立人全血中环孢素A和他克莫司的血药浓度检测方法。对治疗药物监测过程中低、中、高3个浓度水平的质控样品进行统计分析,绘制Levery-Jennings和Z分数质控图,应用Westgard多规则理论进行室内质控评估。结果环孢素A和他克莫司的线性范围分别为10.40~1040.00和0.50~49.50 ng·mL^(-1),定量下限分别为10.40和0.50 ng·mL^(-1),提取回收率分别为108.61%~113.24%和101.99%~109.37%,内标归一化的基质因子分别为106.68%~111.27%和95.70%~97.81%,日内和日间的准确度及精密度均小于15.0%,其他参数也均符合生物样本定量分析要求。Levery-Jennings和Z分数质控图显示,2022年第三季度26组质控样品的检测结果提出警告4次(违反12s规则),未出现失控现象。结论建立的环孢素A和他克莫司治疗药物监测室内质控体系能够有效保障血药浓度检测的准确性。
Objective To establish a quality control method for monitoring the blood concentrations of cyclosporin A and tacrolimus by HPLC-MS/MS,and to evaluate the quality control samples using the Westgard multi-rule theory.Methods HPLC-MS/MS was used to determine the concentration of cyclosporin A and tacrolimus in human whole blood.The quality control samples of low,medium and high concentration levels in the therapeutic drug monitoring process were statistically analyzed,Levery-Jennings and Z-score quality control charts were drawn,and the Westgard multi-rule theory was applied for in-house quality control evaluation.Results The established method was fully validated with linear ranges of 10.40-1040.00 ng·mL^(-1) and 0.50-49.50 ng·mL^(-1),the quantification limits were 10.40 and 0.50 ng·mL^(-1),respectively.The extraction recoveries were 108.61%-113.24%and 101.99%-109.37%,respectively.The matrix factors normalized by internal standard were 106.68%-111.27%and 95.70%-97.81%for cyclosporin A and tacrolimus,respectively.The intra-day and inter-day accuracy and precision were less than 15.0%.Other parameters were also validated and met the acceptance criteria.Levery-Jennings and Z-score quality control charts showed that there were 4 warnings(violation of the 12s rule)in the results of the 26 groups of quality control samples in the third quarter of 2022,and no phenomenon was observed to be out of control.Conclusion The established in-house quality control system for therapeutic drug monitoring of cyclosporin A and tacrolimus can effectively ensure the accuracy of blood drug concentration detection.
作者
钟里科
米秀芳
舒琦
许高奇
何超能
朱俊峰
ZHONG Like;MI Xiufang;SHU Qi;XU Gaoqi;HE Chaoneng;ZHU Junfeng(Department of Pharmacy,Zhejiang Cancer Hospital,Hangzhou Institute of Medicine(HIM),Chinese Academy of Sciences,Hangzhou 310022,China)
出处
《医药导报》
北大核心
2024年第2期196-202,共7页
Herald of Medicine
关键词
环孢素A
他克莫司
高效液相色谱-串联质谱
治疗药物监测
Westgard多规则理论
质控图
Cyclosporin A
Tacrolimus
High-performance liquid chromatography-tandem mass spectrometry
Therapeutic drug monitoring
Westgard multi-rule theory
Quality control chart
