液相色谱-串联质谱法测定地高辛及其室间质量评价

doi:10.3969/j.issn.1673-8640.2015.05.007

检验医学 ›› 2015, Vol. 30 ›› Issue (5): 437-441.DOI: 10.3969/j.issn.1673-8640.2015.05.007

• 质谱技术在临床生化检验中的应用专题 • 上一篇下一篇

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

收稿日期:2015-01-23 出版日期:2015-05-30 发布日期:2015-06-17
作者简介:null
作者简介:孙贺伟,男,1991年生,学士,主要从事质谱技术生物分析工作。

通讯作者:李水军,联系电话:021-54031835。
基金资助:
上海市药学会科研基金资助项目(2014-YY-02-19)

Liquid chromatography-tandem mass spectrometry for the determination of serum digoxin and its external quality assessment

SUN Hewei¹, LIU Haiming², LI Shuijun², YU Chen², ZHU Jianmin²

1. Biological College, Shanghai University, Shanghai 200444, China
2. Central Laboratory, Shanghai Xuhui Central Hospital (Shanghai Clinical Research Center, Chinese Academy of Sciences), Shanghai 200031, China

Received:2015-01-23 Online:2015-05-30 Published:2015-06-17

摘要/Abstract

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Y_LC-MS/MS=1.01X_EQA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

Abstract: Objective To establish a liquid chromatography-tandem mass spectrometry(LC-MS/MS)for therapeutic drug monitoring(TDM)of serum digoxin. Methods An 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. Results The 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 Y_LC-MS/MS=1.01X_{target value}-0.09, r=0.99. Electrochemiluminescence immunoassay results were 36.9% higher on average than those of LC-MS/MS. Conclusions LC-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

中图分类号:

R446.1

孙贺伟, 刘海明, 李水军, 余琛, 朱建民. 液相色谱-串联质谱法测定地高辛及其室间质量评价[J]. 检验医学, 2015, 30(5): 437-441.

SUN Hewei, LIU Haiming, LI Shuijun, YU Chen, ZHU Jianmin. Liquid chromatography-tandem mass spectrometry for the determination of serum digoxin and its external quality assessment[J]. Laboratory Medicine, 2015, 30(5): 437-441.

图/表 5

参考文献 15

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地高辛 (ng/mL)	精密度(%)		准确度(%)		回收率 (%)	基质效应 (%)
地高辛 (ng/mL)	批内	批间			批内	批间
0.05	4.3	/	104.8	/	/	/
0.15	3.6	2.7	108.9	106.1	95.8	95.7
4.00	1.5	1.0	102.9	101.3	97.5	97.6

地高辛 (ng/mL)	精密度(%)		准确度(%)		回收率 (%)	基质效应 (%)
地高辛 (ng/mL)	批内	批间			批内	批间
0.05	4.3	/	104.8	/	/	/
0.15	3.6	2.7	108.9	106.1	95.8	95.7
4.00	1.5	1.0	102.9	101.3	97.5	97.6

地高辛 (ng/mL)	冻融3次 (%)	室温放置 24 h(%)	自动进样器放置36 h(%)
0.15	-8.32	4.28	-0.64
4.00	-1.79	4.16	-0.25

地高辛 (ng/mL)	冻融3次 (%)	室温放置 24 h(%)	自动进样器放置36 h(%)
0.15	-8.32	4.28	-0.64
4.00	-1.79	4.16	-0.25

液相色谱-串联质谱法测定地高辛及其室间质量评价

Liquid chromatography-tandem mass spectrometry for the determination of serum digoxin and its external quality assessment

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