Simultaneous quantification of tenofovir, emtricitabine, rilpivirine, elvitegravir and dolutegravir in mouse biological matrices by LC–MS/MS and its application to a pharmacokinetic study

Pavan Kumar Prathipati, Subhra Mandal, Christopher J. Destache

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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 (r2) 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.

Original languageEnglish (US)
Pages (from-to)473-481
Number of pages9
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume129
DOIs
StatePublished - Sep 10 2016

Fingerprint

Rilpivirine
Tenofovir
Pharmacokinetics
Pharmaceutical Preparations
Tissue
Tissue Distribution
Drug Combinations
Viruses
Application programming interfaces (API)
Mass spectrometry
Assays
Animals
Solid Phase Extraction
Virus Diseases
Liquids
Mass Spectrometry
dolutegravir
JTK 303
Emtricitabine
HIV

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Medicine(all)
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

Cite this

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title = "Simultaneous quantification of tenofovir, emtricitabine, rilpivirine, elvitegravir and dolutegravir in mouse biological matrices by LC–MS/MS and its application to a pharmacokinetic study",
abstract = "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 (r2) 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.",
author = "Prathipati, {Pavan Kumar} and Subhra Mandal and Destache, {Christopher J.}",
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AU - Prathipati, Pavan Kumar

AU - Mandal, Subhra

AU - Destache, Christopher J.

PY - 2016/9/10

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