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 (50mm×2.1mm, 5μm) and mass spectrometric detection by an API 3200 Q Trap instrument. The total run time for each sample was 6min. The method was validated in the concentration range of 5-2000ng/mL for FTC, RPV, DTG, EVG and 10-4000ng/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.
authors: Pharmacy Practice Department, Creighton University School of Pharmacy & Health Professions, Omaha, NE, United States. Electronic address: Pavankumarprathipati@creighton.edu.
authors: Pavan Kumar
authors: PK
authors: Prathipati
authors: Pharmacy Practice Department, Creighton University School of Pharmacy & Health Professions, Omaha, NE, United States.
authors: Subhra
authors: S
authors: Mandal
authors: Pharmacy Practice Department, Creighton University School of Pharmacy & Health Professions, Omaha, NE, United States.
authors: Christopher J
authors: CJ
authors: Destache
mesh_terms: D000818:Animals; D044966:Anti-Retroviral Agents / Q000737:chemistry / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods; D000068679:Emtricitabine / Q000737:chemistry* / Q000493:pharmacokinetics; D005260:Female; D015658:HIV Infections / Q000378:metabolism; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D015363:Quinolones / Q000737:chemistry* / Q000493:pharmacokinetics; D000068696:Rilpivirine / Q000737:chemistry* / Q000493:pharmacokinetics; D052616:Solid Phase Extraction / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods; D000068698:Tenofovir / Q000737:chemistry* / Q000493:pharmacokinetics; D000099226:Dolutegravir
chemical_list: D044966:Anti-Retroviral Agents; D000068679:Emtricitabine; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D015363:Quinolones; D000068696:Rilpivirine; D000068698:Tenofovir; D000099226:Dolutegravir; C509700:elvitegravir
keywords: Antiretroviral; LC–MS/MS; Pharmacokinetic; Plasma; Tissue distribution