HPLC-MS/MS method for the simultaneous quantification of dolutegravir, elvitegravir, rilpivirine, darunavir, ritonavir, raltegravir and raltegravir-β-d-glucuronide in human plasma

Yi Zheng; Radia Aboura; Sana Boujaafar; Gabrielle Lui; Déborah Hirt; Naïm Bouazza; Frantz Foissac; Jean-Marc Treluyer; Sihem Benaboud; Inès Gana

doi:10.1016/j.jpba.2020.113119

HPLC-MS/MS method for the simultaneous quantification of dolutegravir, elvitegravir, rilpivirine, darunavir, ritonavir, raltegravir and raltegravir-β-d-glucuronide in human plasma

J Pharm Biomed Anal. 2020 Apr 15:182:113119. doi: 10.1016/j.jpba.2020.113119. Epub 2020 Jan 18.

Authors

Affiliations

¹ Service de Pharmacologie Clinique, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Groupe Hospitalier Paris Centre, Paris, France; EA 7323, Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris, France; Unité de Recherche Clinique Paris Descartes Necker Cochin, Assistance Publique des Hôpitaux de Paris, Paris, France. Electronic address: zhengyi86@hotmail.fr.
² Service de Pharmacologie Clinique, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Groupe Hospitalier Paris Centre, Paris, France.
³ Service de Pharmacologie Clinique, Hôpital Cochin, Assistance Publique des Hôpitaux de Paris, Groupe Hospitalier Paris Centre, Paris, France; EA 7323, Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris, France; Unité de Recherche Clinique Paris Descartes Necker Cochin, Assistance Publique des Hôpitaux de Paris, Paris, France.
⁴ EA 7323, Université Paris Descartes, Sorbonne Paris Cité, 75006, Paris, France; Unité de Recherche Clinique Paris Descartes Necker Cochin, Assistance Publique des Hôpitaux de Paris, Paris, France.

PMID: 32004775
DOI: 10.1016/j.jpba.2020.113119

Abstract

Therapeutic drug monitoring (TDM) is essential in the optimization of antiretroviral (ARV) treatments. In this work, we describe a new method for the simultaneous quantification of six molecules: the three novel ARV agents dolutegravir (DTG), elvitegravir (ELV) and rilpivirine (RPV), the first integrase inhibitor raltegravir (RAL) and its major metabolite the raltegravir-β-d-glucuronide (RAL-GLU), an protease inhibitor darunavir (DRV) and its booster ritonavir (RTV) in human plasma. The drugs were extracted from 100 μL of plasma by a simple method of protein precipitation using acetonitrile. The separation was carried out on a Kinetex phehyl-hexyl column using a phase mobile composed of 55 % of water (0.05 % formic acid,v/v) and 45 % of methanol (0.05 % formic acid,v/v). The flow rate was set at 0.5 mL/min. The calibration ranged from 60 to 15000 ng/mL for DRV, from 20 to 5000 ng/mL for DTG and ELV, from 10 to 2500 ng/mL for RAL, RAL-GLU, RTV and RPV. The proposed method was validated with a good precision (inter- and intra-day CV% inferior to 12.3 %) and a good accuracy (inter- and intra-day bias between -9.9 % and 10 %) for all the analytes. The proposed method is simple, reliable and suitable for therapeutic drug monitoring (TDM) and for pharmacokinetics studies.

Keywords: Antiretroviral; Liquid chromatography; Tandem mass spectrometry; Therapeutic drug monitoring.

Publication types

Validation Study

MeSH terms

Anti-HIV Agents / analysis*
Anti-HIV Agents / blood
Chromatography, High Pressure Liquid / methods*
Drug Monitoring / methods
Humans
Randomized Controlled Trials as Topic
Reproducibility of Results
Tandem Mass Spectrometry / methods*

Substances

Anti-HIV Agents