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Development of Fast and Simple LC-ESI-MS/MS Technique for the Quantification of Regorafenib; Application to Pharmacokinetics in Healthy Rabbits.

Author(s):

Yatha Ravi*, D.V.R.N. Bhikshapathi, Shankar Cheruku and Bigala Rajkamal  

Abstract:


Background: A simple quantification technique by liquid chromatography–electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) is required for regorafenib in biological matrices with bioavailability studies in healthy rabbits, when compared with reported techniques.

Objective: The main aim of the research work is to develop a validated LC-ESI-MS/MS technique for the quantification of regorafenib and application to bioavailability studies in healthy rabbits.

Methods: Chromatographic separation was achieved with hypersil-C18 analytical column (50mm×4.6 mm, 4µm) and a mobile phase composition of acetonitrile and 5mM ammonium acetate in the proportion of 70:30. The mobile phase was infused into the column with high pressure to get 0.7 ml/min flow rate. The total retention time of the analyte is promising when compared with the existed methods for regorafenib. Quantitation was processed by monitoring transitions of m/z -483.0/262.0 and 450.0/260.0 for regorafenib and internal standard respectively in multiple reaction monitoring.

Results: The linearity equation and correlation coefficient (R2) findings were y =0.9948x+2.6624 and 0.998 respectively. The intra and inter-day precision of the developed technique was found between 1.00 – 8.50% for the QC-samples (2, 4, 240 and 480ng/ml). From bioavailability study, the drug was shown Tmax of 3.688 ± 0.754; average AUC0͢α and AUC0͢t was 6476.81 ± 259.59 and 6213.845 ± 257.892 and Cmax was found to be 676.91 ± 22.045 in healthy rabbits.

Conclusion: The developed technique was validated and successfully applied in the pharmacokinetic study of drug (40 mg tablet) administered through oral route in healthy rabbits.

Keywords:

Regorafenib, Tyrosine Kinase Inhibitor, Bioavailability studies, LC-MS/MS, Matrix effect

Affiliation:

Department of Pharmacy, Mewar University, Chittorgarh, Rajasthan, Department of Pharmaceutics, TRR College of Pharmacy, Hyderabad, Department of Pharmaceutical Analysis, Vijaya College of Pharmacy, Hyderabad, Department of Pharmacy, Mewar University, Chittorgarh, Rajasthan



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