Development and validation of UPLC-MS/MS method for studying the pharmacokinetic interaction of dasabuvir and tamoxifen, 4-hydroxytamoxifen in Wistar rats

Abstract

Hepatitis c virus (HcV) is the main cause of chronic hepatitis and probably liver cirrhosis. Dasabuvir(DSV) is a direct-acting antiviral agent with efficiency in managing HCV. The anti-viral activity of the anti-estrogen drug tamoxifen (TAM) suggested the synergistic effect of DSV and TAM for blocking the replication of HCV. However, being substrates and inhibitors of efflux transporters (TAM inhibits P-gp, DSV inhibits p-gp and BcRp), there is a possibility for a pharmacokinetic (pK) drug-drug interaction. in this work, a new UpLc-MS/MS method was developed and validated for the simultaneous determination of TAM, its active metabolite 4-hydroxy tamoxifen (TOH), and DSV in rat plasma. The method was applied to investigate the pK interaction between DSV and tAM/toH following the coadministration of DSV and TAM to Wistar rats. Chromatographic analysis was performed on Waters BeH tM C18 column using a mobile phase of acetonitrile/water containing 0.1% formic acid (80: 20, v/v). The method allowed the determination of concentration ranges 20-1000, 0.1-500, 0.5-500 ng/mL for DSV, tAM, and toH, respectively. Unexpectedly, results revealed the absence of pK interactions between DSV and tAM/toH, compared with their single administration, suggesting the safety of coadministering DSV/tAM as an anti-viral combination without the need of dosage adjustment.www.nature.com/scientificreports www.nature.com/scientificreports/ Matrix effect. For matrix effect, calculations were based on comparing the peak responses from the four QC samples, used for evaluating the "extraction recovery", spiked post-extraction with those of standard acetonitrile drug solutions prepared of the same nominal concentrations. Scientific RepoRtS |(2020) 10:3521 | https://doi.

Analysis of tamoxifen and its main metabolites in plasma samples of breast cancer survivor female athletes: Multivariate and chemometric optimization

“…Since these compounds are nonvolatile, the use of GC to analyze them requires a derivation step that is extremely time consuming, does not meet the principles of green chemistry, and has not been well received by researchers [10,11]. Hence, LC systems, especially when coupled with MS (LC-MS), are preferred for the analysis of TAM and metabolites in biological samples [10,[14][15][16][17][18][19][20]. However, expensive equipment and materials required for LC-MS use are generally not available in many regular laboratories, especially those in developing countries.…”