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

  • Sci Rep. 2020 Feb 26;10(1):3521. doi: 10.1038/s41598-020-60613-2.
Aliyah Almomen  1 ,  Hadir M Maher  2  3 ,  Nourah Z Alzoman  1 ,  Shereen M Shehata  1 ,  Shorog M Al-Taweel  1 ,  Ashwaq A Alanazi  1
Affiliations
  • 1. College of Pharmacy, Department of Pharmaceutical Chemistry, King Saud University, Riyadh, 11495, P.O. Box 22452, Saudi Arabia.
  • 2. College of Pharmacy, Department of Pharmaceutical Chemistry, King Saud University, Riyadh, 11495, P.O. Box 22452, Saudi Arabia. [email protected].
  • 3. Faculty of Pharmacy, Department of Pharmaceutical Analytical Chemistry, University of Alexandria, El-Messalah, Alexandria, 21521, Egypt. [email protected].
PMID: 32103133 DOI: 10.1038/s41598-020-60613-2
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 co-administration of DSV and TAM to Wistar rats. Chromatographic analysis was performed on Waters BEHTM 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 co-administering DSV/TAM as an anti-viral combination without the need of dosage adjustment.

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