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A Highly Sensitive LC–MS/MS Method Development and Validation of Fedratinib in Human Plasma and Pharmacokinetic Evaluation in Healthy Rabbits

Author(s):

Ayesha Begum K*, G Shiva Kumar, Pamu Sandhya and D.V.R.N. Bhikshapathi   Pages 1 - 10 ( 10 )

Abstract:


Background: A simple and sensitive quantitation analytical technique by liquid chromatography–tandem mass spectrometry (LC-MS/MS) is essential for fedratinib in biological media with kinetic study in healthy rabbits.

Objective: The main objectives of the present research work are to LC-MS/MS method development and validate procedure for the quantitation of fedratinib and its application to kinetic study in rabbits.

Methods: Separation of processed samples were employed on zorbax SB C18 column (50mm×4.6 mm) 3.5µm with a movable phase of methanol, acetonitrile and 0.1% formic acid in the ratio of 30:60:10. The movable phase was monitored through column at 0.8 ml/min flow rate. The drug and ibrutinib internal standard (IS) were evaluated by monitoring the transitions of m/z -525.260/57.07 and 441.2/55.01 for fedratinib and IS respectively in multiple reaction monitoring mode.

Results: The linear equation and coefficient of correlation (R2) results were y =0.00348x+0.00245 and 0.9984 respectively. Intra and inter-day precision %RSD findings of the developed technique were found in the range of 2.4 – 5.3% for the quality control (QC)-samples (252.56, 1804.0 and 2706 ng/ml). The proposed method was subjected for pharmacokinetic study in healthy rabbits and from the kinetic study, fedratinib was shown mean AUClast was 13190±18.1 hr*ng/ml and Cmax was found to be 3550±4.31 ng/ml in healthy rabbits.

Conclusion: The validated method can be applicable for the pharmacokinetic and toxicokinetic studies in the clinical and forensic analysis of fedratinib in different kinds of biological matrices successfully.

Keywords:

Fedratinib, Myelofibrosis, Pharmacokinetics, LC-MS/MS, Accuracy.

Affiliation:

Department of Pharmacy, Gitam University, Hyderabad, Department of Pharmacy, Gitam University, Hyderabad, Department of Pharmaceutics, Shadan Women’s college of Pharmacy, Hyderabad, Department of Pharmaceutics, TRR College of Pharmacy, Hyderabad



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