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液相色谱-大气压化学电离-串联质谱法同时测定人发中的齐多夫定、依非韦伦、洛匹那韦和利托那韦

Simultaneous quantitation of zidovudine, efavirenz, lopinavir and ritonavir in human hair by liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry.

机构信息

Key Laboratory of Child Development and Learning Science (Southeast University), Ministry of Education, and Institute of Child Development and Education, Southeast University, Nanjing 210096, China; School of Biological Sciences & Medical Engineering, Southeast University, Nanjing 210096, China.

Key Laboratory of Child Development and Learning Science (Southeast University), Ministry of Education, and Institute of Child Development and Education, Southeast University, Nanjing 210096, China; School of Public Health, Southeast University, Nanjing 210009, China.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Oct 15;1097-1098:54-63. doi: 10.1016/j.jchromb.2018.08.031. Epub 2018 Sep 4.

DOI:10.1016/j.jchromb.2018.08.031
PMID:30205232
Abstract

Nowadays, zidovudine, efavirenz, lopinavir and ritonavir are important components of the second-line antiretroviral therapeutic regimen of National Free Antiretroviral Treatment Program in China. The measurement of antiretroviral drugs in hair will facilitate for the evaluation of the long-term adherence to highly active antiretroviral therapy. Nevertheless, no study illustrated simultaneous quantitation of the four drugs in hair. The study intended to develop a simple, sensitive and selective method for simultaneous quantitation of the four drugs in hair. The detection employed high liquid chromatography tandem mass spectrometry with atmospheric pressure chemical ionization in positive mode. Hair samples were incubated in methanol at 40 °C for 16 h. The method showed the limit of detection at 18, 8, 5 and 6 pg/mg for zidovudine, efavirenz, lopinavir and ritonavir, respectively. The linear range (R > 0.99) was 36-5000 pg/mg for zidovudine, 16-5000 pg/mg for efavirenz, 10-50,000 pg/mg for lopinavir and 12-12,500 pg/mg for ritonavir. The intra-day and inter-day coefficients of variation were <15% and the recovery varied from 88.1 to 110.5%. The population analysis revealed that patients with high adherence showed significantly higher drug concentrations in hair than those with low adherence for both AZT and EFV (ps < 0.05). There was high association in drug contents in hair between AZT and EFV or LPV and RTV (ps < 0.05).

摘要

如今,齐多夫定、依非韦伦、洛匹那韦和利托那韦是中国国家免费抗逆转录病毒治疗计划二线抗病毒治疗方案的重要组成部分。头发中抗逆转录病毒药物的测定有助于评估长期接受高效抗逆转录病毒治疗的情况。然而,目前尚无研究表明可同时定量检测头发中的这四种药物。本研究旨在建立一种简单、灵敏、选择性的同时定量检测头发中这四种药物的方法。采用大气压化学电离正离子模式的高效液相色谱串联质谱法进行检测。将头发样品在 40°C 的甲醇中孵育 16 小时。该方法对齐多夫定、依非韦伦、洛匹那韦和利托那韦的检测限分别为 18、8、5 和 6pg/mg。齐多夫定的线性范围(R>0.99)为 36-5000pg/mg,依非韦伦为 16-5000pg/mg,洛匹那韦为 10-50,000pg/mg,利托那韦为 12-12,500pg/mg。日内和日间变异系数均<15%,回收率在 88.1-110.5%之间。群体分析显示,高依从性患者的头发中 AZT 和 EFV 的药物浓度明显高于低依从性患者(p<0.05)。AZT 和 EFV 或 LPV 和 RTV 之间的药物含量在头发中具有高度相关性(p<0.05)。

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