孙贺伟，　刘海明，　李水军，　余　琛，　朱建民

[1. 上海大学生命科学学院，上海 200444；

2. 上海市徐汇区中心医院(中国科学院上海临床研究中心)中心实验室，上海 200031]

液相色谱-串联质谱法测定地高辛及其室间质量评价

孙贺伟1，刘海明2，李水军2，余琛2，朱建民2

[1. 上海大学生命科学学院，上海 200444；

2. 上海市徐汇区中心医院(中国科学院上海临床研究中心)中心实验室，上海 200031]

摘要：目的建立液相色谱-串联质谱(LC-MS/MS)检测血清地高辛的方法，用于临床开展地高辛治疗药物监测(TDM)。方法采用同位素稀释LC-MS/MS测定血清地高辛浓度并进行方法学评价。样品采用特丁基甲醚提取，反相色谱分离，正离子电喷雾质谱仪检测。分析参加卫生部临检中心地高辛TDM室间质量评价(EQA)的结果，并与电化学发光法进行初步比较。结果LC-MS/MS的线性范围为0.05～5.00 ng/mL，精密度为1.0%～4.3%，准确度为101.3%～108.9%，回收率为95.8%～97.5%，基质效应为95.7%～97.6%。单份样品的分析检测时间为 3 min。血清样品反复冻融3次、放置室温24 h、处理后放置自动进样器36 h的稳定性良好。EQA样品的LC-MS/MS测定结果与靶值的偏差为-4.09%，线性方程为YLC-MS/MS=1.01XEQA靶值-0.09，r=0.99。电化学发光法测定结果比LC-MS/MS平均高36.9%。结论LC-MS/MS测定血清地高辛简便、特异。测定结果符合全国室间质量评价要求，但与电化学发光法存在较大的差异。

关键词：地高辛；液相色谱-串联质谱法；室间质量评价；电化学发光法

Liquid chromatography-tandem mass spectrometry for the determination of serum digoxin and its external quality assessmentSUNHewei1，LIUHaiming2，LIShuijun2，YUChen2，ZHUJianmin2

.[1.BiologicalCollege，ShanghaiUniversity，Shanghai200444，China; 2.CentralLaboratory，ShanghaiXuhuiCentralHospital(ShanghaiClinicalResearchCenter，ChineseAcademyofSciences)，Shanghai200031，China]

Abstract：ObjectiveTo establish a liquid chromatography-tandem mass spectrometry(LC-MS/MS)for therapeutic drug monitoring(TDM)of serum digoxin. MethodsAn isotope dilution LC-MS/MS was realized by tert-butyl methyl ether extraction， reversed-phase separation and positive electrospray ionization mass spectrometry detection. The results of external quality assessment(EQA)of digoxin TDM program of the National Center for Clinical Laboratory by LC-MS/MS were analyzed and compared with those of electrochemiluminescence immunoassay. ResultsThe linear range was 0.05-5.00 ng/mL. The precision was 1.0%-4.3%, and the accuracy was 101.3%-108.9%. The recovery rate was 95.8%-97.5%, and the matrix effect was 95.7%-97.6%. The total run time was 3 min per injection. Good stability was observed on serum undergoing 3 cycles of frozen-thaw， at room temperature for 24 h and pretreating serum placed in autosampler for 36 h. The average bias was -4.09% between LC-MS/MS and the target value of EQA with a correlation formula of YLC-MS/MS=1.01Xtarget value-0.09， r=0.99. Electrochemiluminescence immunoassay results were 36.9% higher on average than those of LC-MS/MS. ConclusionsLC-MS/MS is simple and specific for the determination of serum digoxin. The results reported by LC-MS/MS are comparable with the national external quality assessment proficiency test. There is significant difference in digoxin results between LC-MS/MS and electrochemiluminescence immunoassay.

Key words：Digoxin; Liquid chromatography-tandem mass spectrometry; External quality assessment; Electrochemiluminescence immunoassay

地高辛是临床抗心力衰竭的常用药物，但其毒副作用大，安全范围窄，药物代谢动力学、药物效应动力学个体差异大，且治疗剂量与中毒剂量相互重叠，易发生中毒反应[1-2]。……