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  2. Validated UPLC-MS/MS method for the quantification of dasatinib in plasma: Application to pharmacokinetic interaction studies with nutraceuticals in Wistar rats

Validated UPLC-MS/MS method for the quantification of dasatinib in plasma: Application to pharmacokinetic interaction studies with nutraceuticals in Wistar rats

  • PLoS One. 2018 Jun 14;13(6):e0199208. doi: 10.1371/journal.pone.0199208.
Hadir M Maher 1 2 Nourah Z Alzoman 1 Shereen M Shehata 1 Norah O Abanmy 3
Affiliations

Affiliations

  • 1 College of Pharmacy, Department of Pharmaceutical Chemistry, King Saud University, Riyadh, Saudi Arabia.
  • 2 Faculty of Pharmacy, Department of Pharmaceutical Analytical Chemistry, University of Alexandria, El-Messalah, Alexandria, Egypt.
  • 3 College of Pharmacy, Department of Clinical Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Abstract

Dasatinib (DAS) is a tyrosine kinase inhibitor (TKI) used in the treatment of chronic myeloid leukemia and in the management of ulcerative colitis (UC). Since some nutraceuticals (e.g. curcumin, olive oil, and cocoa extract) could alter the function of ABC transporters and /or CYP450 enzymes, DAS bioavailability could potentially be affected following their co-administration. This work aims at studying the possibility of PK interaction between DAS and the selected nutraceuticals in UC rats using UPLC- MS/MS. Chromatographic analysis was carried out using BEH C 18 column (Waters) with a mobile phase consisting of acetonitrile and 50% aqueous methanol, 65:35, v/v, each with 0.1% formic acid and using erlotinib (ERL) as an internal standard (IS). DAS quantitation was carried out using multiple reaction monitoring (MRM) with positive ionization of the transitions at m/z 488.03 > 400.92 (DAS), and m/z 394.29 > 278.19 (ERL). Method validation was assessed as per the FDA guidelines for bioanalytical methods for DAS determination within the concentration range 1-500 ng/mL. No significant effect on the oral bioavailability of DAS was reported with any of the studied nutraceuticals. Thus, the concomitant administration of these nutraceuticals with DAS could be considered safe with a necessity to perform more detailed clinical investigations.

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