Quantification of darunavir and etravirine in human peripheral blood mononuclear cells using high performance liquid chromatography tandem mass spectrometry (LC-MS/MS), clinical application in a cohort of 110 HIV-1 infected patients and evidence of a potential drug-drug interaction.

摘要: Abstract Objectives To describe the validation of a sensitive high performance liquid chromatography tandem mass spectrometry (LC–MS/MS) method allowing simultaneous quantification darunavir (DRV) and etravirine (ETR) in peripheral blood mononuclear cells (PBMCs) its application cohort HIV-1 infected patients. Methods Blood samples were obtained from 110 PMBCs isolated using density gradient centrifugation. Drug extraction PBMCs was performed with 60:40 methanol–water (MeOH–H2O) solution containing deuterated IS (DRV-d9 ETR-d8). The chromatographic separation on RP18 XBridge™ column. Results geometric mean (GM) cell associated concentration ([DRV]CC) plasmatic ([DRV]plasma) 360.5 ng/mL (CI95%:294.5–441.2) 1733 ng/mL (CI95%:1486–2021), respectively. A intracellular (IC)/plasma ratio (GMR) 0.21 (CI95%:0.18–0.24) calculated. Adjusted for dose/body surface area post-intake time, statistically significant correlation observed between [DRV]Plasma eGFR (p = 0.002) concomitant use ETR (p = 0.038). For 10 patients receiving addition to DRV, GM [ETR]Plasma (available 8 out patients) [ETR]CC 492.3 ng/mL 2951 ng/mL GMR 7.6 (CI95%: 3.61–13.83). Conclusions handy LC–MS/MS DRV has been described successfully applied largest DRV-treated reported date. accumulates more efficiently compared DRV. We have also highlighted possible impact plasma concentrations requiring further investigations.