Development and validation of an ultra-high performance liquid chromatography-tandem mass spectrometry method to quantify antiretroviral drug concentrations in human plasma for therapeutic monitoring.

Autor: West RE 3rd; Center for Clinical Pharmaceutical Sciences, Department of Pharmacy & Therapeutics, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA., Oberly PJ; Center for Clinical Pharmaceutical Sciences, Department of Pharmacy & Therapeutics, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA., Riddler SA; Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Nolin TD; Center for Clinical Pharmaceutical Sciences, Department of Pharmacy & Therapeutics, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA., Devanathan AS; Center for Clinical Pharmaceutical Sciences, Department of Pharmacy & Therapeutics, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: asd129@pitt.edu.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2024 Mar 15; Vol. 240, pp. 115932. Date of Electronic Publication: 2023 Dec 30.
DOI: 10.1016/j.jpba.2023.115932
Abstrakt: Antiretroviral therapy (ART) is highly effective for the treatment of HIV-1 infection. ART previously consisted of concomitant administration of many drugs, multiple times per day. Currently, ART generally consists of two- or three-drug regimens once daily as fixed-dose combinations. Drug monitoring may be necessary to ensure adequate concentrations are achieved in the plasma over the dosing interval and prevent further HIV resistance formation. Additionally, nonadherence remains an issue, highlighting the need to ensure sufficient ART exposure. Towards this effort, we developed and validated a highly selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of a panel of nine antiretrovirals: abacavir, bictegravir, cabotegravir, dolutegravir, doravirine, emtricitabine, lamivudine, raltegravir, and tenofovir in human plasma. Using only 50 µL of plasma, a simple protein precipitation with acetonitrile with internal standards followed by reconstitution in 50 uL (high) or 400 uL (low) was performed. Analyte separation was achieved using a multistep UPLC gradient mixture of (A: 0.1% formic acid in water and B: acetonitrile) and a Waters CORTECS T3 (2.1 ×100 mm) column. The method was comprehensively validated according to the United States Food and Drug Administration Bioanalytical Guidelines over two clinically relevant ranges (1-250 ng/mL and 100-5000 ng/mL) with excellent linearity (R 2 > 0.99 for all). The assay run time was 7.5 min. This method achieves acceptable performance of trueness (89.7-104.1%), repeatability, and precision (CV <15%), and allows for simultaneous quantification of guideline-recommended ART regimens. This method can be utilized for the therapeutic monitoring of antiretrovirals in human plasma.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sharon A. Riddler reports a relationship with Gilead Sciences Inc that includes: funding grants. Sharon A. Riddler reports a relationship with Merck & Co Inc that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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