Submit Manuscript  

Article Details


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

[ Vol. 17 , Issue. 6 ]

Author(s):

Ayesha Begum Khadernaick*, Gubbiyappa Shiva Kumar, Pamu Sandhya and Darna Bhikshapathi   Pages 782 - 791 ( 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 the development of the LC-MS/MS method and to validate a procedure for the quantitation of fedratinib and its application to kinetic study in rabbits.

Methods: Separation of processed samples was done 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 to pharmacokinetic study in healthy rabbits and the kinetic study, fedratinib showed mean AUClast 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, phosphorylation.

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

Graphical Abstract:



Read Full-Text article