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A validated reverse phase stability-indicating HPLC method for bortezomib in the presence of degradation products and its process-related impurities
- Author Details:
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Jagadeswara Rao K
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Mohan B
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Venugopal NVS
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Murali Mohan SV
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Rama Rao Malla
Degradation pathway of bortezomib was established as per ICH recommendations in terms of validated and stability indicating reverse phase liquid chromatographic method. Bortezomib was subjected to stress using conditions of acid, base, oxidation, thermal and photolysis. Significant degradation was observed in acid and base stress conditions. Ten impurities were studied and the major degradant was hydroxyamide impurity. The stress samples were assayed against a qualified reference standard and the mass balance is found close to 98.2%. Efficient chromatographic separation was achieved on a Zorbax Extend C18(100 x 4.6 mm, 1.8 ?m) stationary phase with simple mobile phase combination In the developed LC method, the resolution between bortezomib and ten potential impurities such as Imp-A, Imp-B, Imp-C, Imp-D, Imp-E, Imp-F, Imp-G, bortezomib isomer, hydroxyamide and bortezomib ester) was found to be greater than 2.0. Regression analysis showed r value (correlation coefficient) of greater than 0.999 for bortezomib and ten potential impurities. This method was capable of detecting the impurities of bortezomib at a level of 0.02% with respect to test concentration of 2.0 mg/mL. The developed rapid LC method was validated with respect to specificity, linearity, range, accuracy, precision and robustness for impurities.
Keywords: Bortezomib, Analytical Method development, Analytical Method validation and High Performance Liquid Chromatography
References
- Richardson PG, Mitsiades C, Schlossman R. Bortezomib in the frontline treatment of multiple myeloma. Expert Review of Anticancer Therapy 2008:8:1053–1072.
- Mikhael J, Chang H. Bortezomib: proteasome inhibition as a novel mechanism of cancer therapy-implications for hematological malignancies. Letters in Drug Design & Discovery 2007;4:82–86.
- Kasa Srinivasulu, Mopidevi Narasimha Naidu, Kadaboina Rajasekhar, Murki Veerender, Mukukutla Venkata Suryanarayana. Development and validation of a Stability indicating LC method for the Assay and related substances determination of a Proteasome Inhibitor. 2012:2012:13.
- Smith MB, March J. March's Advanced Organic Chemistry, John Wiley &Sons, Hoboken, NJ, USA, 6th edition,2007.
- Pitt B, Remme W, Zannad F, Bortezomib Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators, ACC Current Journal Review. 2003;12:57B.
- Venkataramanna M, Sudhakar Babu K, Anwar sulaiman KC. A validated stability-Indicating UF LC method for Bortezomib in the presence of degradation products and its process- related impurities. 2012:2.
- Utage M, Dr. Swamy BMV. Stability indicating HPLC Method for Estimation of Bortezomib for injection 3.5 mg/ vial. 2013:2:2
- Burgess E, Niegowksa J, Tan KW, Kipnes MS, Roniker B, Patrick J. L, et al. Bortezomib 016 Investigators American Journal of Hypertension. Volume 15, Issue 2002; 1: A23, A57-A58.
- Bruce A, Pearlman, Amphlett G, Padilla, John T, Hach, Jeffrey L, et al. Havens, and Muniraj D, Pillai A, New Approach to the Furan Degradation Problem Involving ozonolysis of the trans- Enedione and Its Use in a Cost- Effective Synthesis of Bortezomib Chemical Research Jagadeswara Rao K et al. A validated reverse phase stability-indicating HPLC method for…. International Journal of Pharmaceutical Chemistry and Analysis, 3(3):150-161 161 and Development, Pfizer, Incorporated, Kalamazoo, Michigan. 2006:8:2111–2113.
- Zhang Ji Y, Douglas M Fast, Alan P. Bureau, Journal of Chromatography B. 2003:787:333-344.
- Rane VP, Patil KR, Sangshetti JN, Yeole RDV, Shinde DB. Stability-indicating RP-HPLC method for analysis of bortezomib in the bulk drug and in a pharmaceutical dosage form.2009:21:619-629.
- ICH Q2 (R1), Validation of analytical procedures: Text and methodology, 2005.
- ICH Q1 (R2), Stability testing of New Drug Substances and Products, 2000.
- ICH, Photo stability testing of new drug substances and products Q1B.
- Singh S, Bakshi M. 200:24:1-14.
- ICH Guidelines on validation of analytical Procedures definitions and terminology.
- Drug stability principles and practices third edition, edited by Jens T, Carstensen Rhodes CT. 2000.
- Bakshi M, Singh S, Development of validated stability indicating assay methods critical review. J Pharm Biomed. 2002:28:1011-1040.
- Validation of compendial methods The United States Pharmacopeia.2016:42.
- Jens T, Carstensen, Rhodes CT, Drug stability principles and practices, Marcel Dekker, New York, 2000.
- ICH Stability Testing of New Drug Substances and Products Q1A (R2), International Conference on Harmonization, IFPMA, Geneva, 2003.
How to Cite This Article
Vancouver
K JR, B M, NVS V, SV MM, Malla RR. A validated reverse phase stability-indicating HPLC method for bortezomib in the presence of degradation products and its process-related impurities [Internet]. Int J Pharm Chem Anal. 2016 [cited 2025 Oct 23];3(3):150-161. Available from: https://doi.org/
APA
K, J. R., B, M., NVS, V., SV, M. M., Malla, R. R. (2016). A validated reverse phase stability-indicating HPLC method for bortezomib in the presence of degradation products and its process-related impurities. Int J Pharm Chem Anal, 3(3), 150-161. https://doi.org/
MLA
K, Jagadeswara Rao, B, Mohan, NVS, Venugopal, SV, Murali Mohan, Malla, Rama Rao. "A validated reverse phase stability-indicating HPLC method for bortezomib in the presence of degradation products and its process-related impurities." Int J Pharm Chem Anal, vol. 3, no. 3, 2016, pp. 150-161. https://doi.org/
Chicago
K, J. R., B, M., NVS, V., SV, M. M., Malla, R. R.. "A validated reverse phase stability-indicating HPLC method for bortezomib in the presence of degradation products and its process-related impurities." Int J Pharm Chem Anal 3, no. 3 (2016): 150-161. https://doi.org/