LC-QQQ-MS based intracellular quantification of bictegravir in peripheral blood mononuclear cells and plasma

Most antiretrovirals (ARVs) have intracellular therapeutic target sites and therefore, their plasma concentration may be misleading when relating to their efficacy or toxicity. A bioanalytical method for quantification of the ARV drug bictegravir (BTG) in its target site peripheral blood mononuclear cells (PBMCs) is not available till date. This is the first time to establish a sufficiently sensitive mass spectrometry-based bioanalytical method to quantify BTG in both rat PBMCs and plasma. The developed method was validated over the range of 1 ng/ml to 100 ng/ml and 0.005 ng–10ng/sample for plasma and PBMCs, respectively. For PBMCs, average accuracy and precision at four quality control levels were found to be 93.30%–110.00% and 6.52%–8.25%, respectively. Plasma and intracellular pharmacokinetics of BTG was evaluated by the developed method in rats and a lack of accumulation of BTG in the PBMCs was observed. Pearson correlation coefficient data analysis indicated a moderated correlation between plasma and PBMC concentration of BTG. Therefore, it will be beneficial to include a quantification plan for BTG in its actual therapeutic target site during all its future research and development work. This reported method can be useful for site-specific monitoring of BTG in research laboratories and pharmaceutical industries. [Display omitted] •Intracellular estimation reflects actual availability of ARVs at target site.•Established a LC-QQQ-MS method to quantify bictegravir in PBMCs.•Optimized the isolation procedure of rat PBMCs from whole blood.•Evaluated plasma and intracellular pharmacokinetic of bictegravir.