BIOANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF IBRUTINIB IN BIOLOGICAL MATRICES BY LC-MS/MS
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.
2. Vries R. Stable isotope-labeled intravenous microdose for absolute bioavailability and effect of grapefruit juice on ibrutinib in healthy adults. Br J Clin Pharmacol 2016;81:235–45.
3. Ponader S, Chen SS, Buggy JJ, Balakrishnan K, Gandhi V, Wierda WG, et al. The bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Blood 2012;119:1182–9.
4. Rooij MF, Kuil A, Geest CR, Eldering E, Chang BY, Buggy JJ, et al. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor-and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia 2012;119:2590–4.
5. Pavlasova G. Ibrutinib inhibits CD20 upregulation on CLL B cells mediated by the CXCR4/SDF-1 axis. Blood 2016;128: 1609–13.
6. Seda V, Mraz M. B-cell receptor signalling and its crosstalk with other pathways in normal and malignant cells. Eur J Haematol 2016;94:193–205.
7. Brown JR. Ibrutinib (PCI-32765), the first BTK (Bruton’s tytosine kinase) inhibitor in clinical trials. Curr Hematol Malig Rep 2016;8:1–6.
8. Walker, Joseph. Patients struggle with high drug prices: out-of-pocket costs for pricey new drugs leave even some insured and relatively affluent patients with hard choices on how to afford them. Wall Street J; 2016.
9. Sureshbabu Kapavarapu, Ramu Golkonda, Rambabu Chintala. Validation of stability indicating RP-HPLC method for the assay of Ibrutinib in the pharmaceutical dosage form. Anal Chem An Indian J 2016;16:7-19.
10. Vykuntam U, Divya E, Charishma K, Harshavardan, Shyamala M. Validated stability-indicating RP-HPLC method for determination of ibrutinib. Indo Am J Pharm Sci 2016;3:324-30.
11. Muneer S, Abdul Ahmad, Chandrasekhar. A novel stability indicating analytical development and validation of a RP-HPLC assay method for the quantification of ibrutinib in bulk and its formulation. J Pharm Res 2017;11:712-8.
12. Li-min WEI, Zhen Xing, Peng Fei, Yong-le, Xiang-Xiang, Min ZHANGA. Simple HPLC method for the determination of ibrutinib in rabbit plasma and its application to a pharmacokinetic study. Latt Am J Pharm 2016;35:130-4.
13. Veeraraghavan S, Viswanadha S, Thappali S, Govindarajulu B, Vakkalanka S, Rangasamy M. Simultaneous quantification of lenalidomide, Ibrutinib and its active metabolite PCI-45227 in rat plasma by LC-MS/MS: application to a pharmacokinetic study. J Pharm Biomed Anal 2015;107:151-8.
14. US FDA, Guidance for Industry Bioanalytical Method Validation, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Rockville, Maryland, USA; 2001.
15. Tijare LK, Rangari NT, Mahajan UN. A review on bioanalytical method development and validation. Asian J Pharm Clin Res 2016;9:6-10.
16. Liliya Logoyda, Dmytro Korobko, Oleksandra Oleshchuk, Taras Proniv, Mariya Dmutriv. A HPLC-MS/MS method development and validation for the simultaneous determination of bisoprolol and enalapril in the present of enalaprilat in human plasma. Int J Appl Pharm 2018;10:31-40.
17. Swathi P, Vidyadhara S, Sasidhar RLC, Kalyan Chakravarthi K. Method development and validation for the estimation of entecavir in bulk and pharmaceutical dosage forms by RP-HPLC. Int J Curr Pharm Res 2017;9:107-11.
18. ICH: Q2B. Harmonized Tripartite Guideline, Validation of Analytical Procedure: Methodology, IFPMA, in Proceedings of the International Conference on Harmonization, Geneva; 1996.
19. ICH: Q2 (R1), Validation of analytical procedures: text and methodology; 2005.
20. Revathi Naga, Lakshmi Ponnuri, Prahlad Pragallapati, Ravindra N, Venkata Basaveswara, Rao Mandava. A rapid and sensitive liquid chromatography-mass spectrometry/mass spectrometry method for estimation of pioglitazone, keto pioglitazone and hydroxy pioglitazone in human plasma. Asian J Pharm Clin Res 2017;10:120-8.