Validation of a fast method for quantitative analysis of elvitegravir, raltegravir, maraviroc, etravirine, tenofovir, boceprevir and 10 other antiretroviral agents in human plasma samples with a new UPLC-MS/MS technology

详细信息    查看全文

• 作者：Zoubir Djerada ; Catherine Feliu ; Claire Tournois ; Damien Vautier ; Laurent Binet ; Arnaud Robinet ; H¨¦l¨¨ne Marty ; Claire Gozalo ; Denis Lamiable ; Herv¨¦ Millart
• 关键词：ARV ; antiretroviral drugs ; IS ; internal standard ; Ct ; plasma trough concentration ; MRM ; multiple reaction transition ; TDM ; therapeutic drug monitoring ; UPLC-MS/MS ; ultra-performance liquid chromatography-tandem mass spectrometry
• 刊名：Journal of Pharmaceutical and Biomedical Analysis
• 出版年：2013
• 出版时间：December, 2013
• 年：2013
• 卷：86
• 期：Complete
• 页码：100-111
• 全文大小：1148 K

文摘

Therapeutic drug monitoring (TDM) of antiretrovirals requires accurate and precise analysis of plasma drug concentrations. This work describes a simple, fast and sensitive UPLC-MS/MS method for determination of the commonly used protease inhibitors such as amprenavir, atazanavir, darunavir, indinavir, lopinavir, ritonavir, saquinavir and tipranavir, tenofovir a nucleoside reverse transcriptase inhibitor (NRTI), the non-NRTI such as efavirenz, nevirapine, etravirine, the CCR5 antagonist maraviroc as well as the more recent antiretrovirals, the integrase inhibitors such as raltegravir, elvitegravir and the new direct acting anti-HCV boceprevir. Adapted deuterated internal standard was added to plasma aliquots (100 ¦Ìl) prior to protein precipitation with methanol and acetonitrile. This method employed ultra-performance liquid chromatography coupled to tandem mass spectrometry with electrospray ionization mode. All compounds eluted within 4.2-min run time. Calibration curves were validated, with correlation coefficients (r²) higher than 0.997, for analysis of therapeutic concentrations reported in the literature. Inter- and intra-assay variations were <15 % . Evaluation of accuracy shows a deviation <15 % from target concentration at each quality control level. No significant matrix effect was observed for any of the antiretroviral studied. This new validated method fulfills all criteria for TDM of 15 antiretrovirals and boceprevir drugs and was successfully applied in routine TDM of antiretrovirals.