TY - JOUR
T1 - Simultaneous quantification of tenofovir, emtricitabine, rilpivirine, elvitegravir and dolutegravir in mouse biological matrices by LC–MS/MS and its application to a pharmacokinetic study
AU - Prathipati, Pavan Kumar
AU - Mandal, Subhra
AU - Destache, Christopher J.
N1 - Funding Information:
This work was supported by NIH grant RO1 AI117740-01 to C.J.D. The Animal Research Facility is supported by Grant Number G20RR024001 from the National Center for Research Resources . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.
PY - 2016/9/10
Y1 - 2016/9/10
N2 - Combination antiretroviral (cARV) treatment is more common in human immunodeficiency virus (HIV) infection. In many instances, treatment regimen includes two or more combination of drugs from six different classes. Some of the antiretroviral combination medications are under study at preclinical and clinical stages. A precise method is required to quantify the drug concentration in biological matrices to study pharmacokinetic behavior and tissue distribution profile in animals and/or humans. We have developed and validated a sensitive and precise liquid chromatography–tandem mass spectrometry method for simultaneous quantification of selected antiretroviral drugs, tenofovir (TNF), emtricitabine (FTC), rilpivirine (RPV), dolutegravir (DTG) and elvitegravir (EVG) in mouse biological matrices. This method involves a solid phase extraction, simple isocratic chromatographic separation using Restek Pinnacle DB BiPh column (50 mm × 2.1 mm, 5 μm) and mass spectrometric detection by an API 3200 Q Trap instrument. The total run time for each sample was 6 min. The method was validated in the concentration range of 5–2000 ng/mL for FTC, RPV, DTG, EVG and 10–4000 ng/mL for TNF respectively with correlation coefficients (r 2 ) higher than 0.9976. The results of intra and inter-run assay precision and accuracy were within acceptance limits for all the five analytes. This method was used to support the study of pharmacokinetics and tissue distribution profile of nanoformulated antiretroviral drugs in mice.
AB - Combination antiretroviral (cARV) treatment is more common in human immunodeficiency virus (HIV) infection. In many instances, treatment regimen includes two or more combination of drugs from six different classes. Some of the antiretroviral combination medications are under study at preclinical and clinical stages. A precise method is required to quantify the drug concentration in biological matrices to study pharmacokinetic behavior and tissue distribution profile in animals and/or humans. We have developed and validated a sensitive and precise liquid chromatography–tandem mass spectrometry method for simultaneous quantification of selected antiretroviral drugs, tenofovir (TNF), emtricitabine (FTC), rilpivirine (RPV), dolutegravir (DTG) and elvitegravir (EVG) in mouse biological matrices. This method involves a solid phase extraction, simple isocratic chromatographic separation using Restek Pinnacle DB BiPh column (50 mm × 2.1 mm, 5 μm) and mass spectrometric detection by an API 3200 Q Trap instrument. The total run time for each sample was 6 min. The method was validated in the concentration range of 5–2000 ng/mL for FTC, RPV, DTG, EVG and 10–4000 ng/mL for TNF respectively with correlation coefficients (r 2 ) higher than 0.9976. The results of intra and inter-run assay precision and accuracy were within acceptance limits for all the five analytes. This method was used to support the study of pharmacokinetics and tissue distribution profile of nanoformulated antiretroviral drugs in mice.
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U2 - 10.1016/j.jpba.2016.07.040
DO - 10.1016/j.jpba.2016.07.040
M3 - Article
C2 - 27497648
AN - SCOPUS:84982732947
VL - 129
SP - 473
EP - 481
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
SN - 0731-7085
ER -