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

Publication date: Available online 18 January 2020Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Yi Zheng, Radia Aboura, Sana Boujaafar, Gabrielle Lui, Déborah Hirt, Naïm Bouazza, Frantz Foissac, Jean-Marc Treluyer, Sihem Benaboud, Inès GanaAbstractTherapeutic 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 the...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research