BIOANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF IBRUTINIB IN BIOLOGICAL MATRICES BY LC-MS/MS

N. J. R. HEPSEBAH; A. ASHOK KUMAR

doi:10.22159/ijpps.2019v11i3.31034

Authors

N. J. R. HEPSEBAH Mewar University, Chittorgarh, Rajasthan, India
A. ASHOK KUMAR Mewar University, Chittorgarh, Rajasthan, India

DOI:

https://doi.org/10.22159/ijpps.2019v11i3.31034

Keywords:

Ibrutinib, Chronic lymphocytic leukemia, LC-MSMS, FDA guidelines, and, Dilution integrity

Abstract

Objective: The main aim of the research was to develop a fast and highly sensitive bioanalytical LC-MS/MS technique for the quantitation of ibrutinib in human plasma.

Methods: Chromatography has achieved on a reverse phase-symmetry C₁₈(75 mm × 4.6 mm, 3.5 µm) column with gradient elution by acetonitrile, methanol and 0.1%v/v formic acid as the mobile phase. Chromatographic peaks were resolved with 0.7 ml/min flow rate. Drug was extracted with ethyl acetate solvent by liquid-liquid extraction method. Monitoring of transition of m/z 441.2 and 55.01 for ibrutinib and 446.5 and 60.01 for Ibrutinib-D5 were made on multiple reaction monitoring.

Results: Calibration curve of ibrutinib was linear over 1-600 ng/ml concentration range with a regression coefficient (r²) value of>0.99. The % RSD values were less than 8.5% for inter-day and intra-day precision and accuracy. The method has excellent recovery and the percentage recovery values of lower quality control (LQC), median quality control (MQC) and higher quality control (HQC) samples were 101.86%, 102.8%, and 99.28% respectively.

Conclusion: The drug was stable for more time at variable stability conditions and method was successfully applicable to the regular analysis of ibrutinib in biological matrices.

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