UPLC–MS/MS method with automated on-line SPE for the isomer-specific quantification of the first-generation anti-HCV protease inhibitors in peripheral blood mononuclear cells

Publication date: 10 November 2015 Source:Journal of Pharmaceutical and Biomedical Analysis, Volume 115 Author(s): Amedeo De Nicolò, Adnan Mohamed Abdi, Lucio Boglione, Lorena Baiett, Sarah Allegra, Giovanni Di Perri, Antonio D’Avolio HCV infection affects over 170 million people worldwide. The current standard for treatment of genotype 1 infection is the association of the first generation protease inhibitors boceprevir or telaprevir to ribavirin and peginterferon α. Although the response rate has been improved with these new drugs, some pharmacokinetic/pharmacodinamic issues emerged in the past years. To date, some analytical methods are available for the quantification of these drugs in plasma; however, the real active concentrations of the two drugs are those in hepatocytes. Being the withdrawal of hepatocytes too invasive, in this work we aimed to develop and validate a chromatographic method coupled with tandem mass spectrometry capable of quantifying boceprevir and telaprevir isomers in peripheral blood mononuclear cells, used as an “in-vivo” cellular model of compartmentalization. The method used an on-line solid phase extraction protocol based on the new OSM® platform and was fully validated following FDA guidelines. This method showed mean intra- and inter-day inaccuracy and imprecision both lower than 15%, high and stable recovery and contained matrix effect, with a run time of 6min, comprehensive of SPE extraction. The method was then ap...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research