Development of a stability-indicating method for evaluation of impurity profile of Atorvastatin film-coated tablets using cyano column based on core-shell technology
Keywords:forced degradation study, atorvastatin, stability-indicating method, cyano fused-core shell column
This research highlights the specificity of the new stability-indicating method developed to evaluate the impurity profile of Atorvastatin film-coated tablets. The proposed method has the ability to capture any possible changes that may occur during the stability studies over time and under different stress factors, and is selective enough to enable quality control of finished product from different suppliers of active pharmaceutical ingredient (API)/excipients.
Satisfactory critical peak resolution between specified and unspecified impurities was achieved using the fused-core shell technology and extensively endcapped diisopropyl-cyanopropylsilane stationary phase (Halo ES-CN 150 mm × 4.6 mm, 2.7 µm), with a 10 mM ammonium formate buffer pH 3.5 and acetonitrile as mobile phase. A potential worse case impurity profile was assumed by using retained samples combined with the data obtained for samples manufactured with APIs from different suppliers exposed to the forced degradation study. The mass balance for stressed samples demonstrated the stability-indicating capability of the proposed method.
(1) European Pharmacopoeia 10.0 edition (volume 10.4) Strasbourg Cedex: Council of Europe, Chapter 14, Monograph 04/2021:2191, 5425–5427, 2021.
(2) Atorvastatin: Uses, Interactions, Mechanism of Action | DrugBank Online.
(3) Mallu, U. R.; Nair, A. K.; Sankar, J.; Bapatu, H. R.; Kumar, M. P.; Naria, S.; Bhanap, T. A.; Thamma, N. K., NVVSS Raman Impact of API source selection on generic drug product, Pharmaceutical Regulatory Af-fairs 2015, 4 (2). DOI: 10.4172/2167-7689.1000136.
(4) Jakaria, Md.; Chowdhury, T. A.; Bhuiyan, Ari-fujjaman, D. I.; Mamur, A., Effect of acid, base and heat on five brands of Atorvastatin tablets available in Bangladesh, Journal of Scientific and Innovative Re-search, 2014, 3 (6), 598–601.
(5) Singh, R.; Rehman, Z., Current trends in forced degra-dation study for pharmaceutical product development, J. Pharm Edu. 2012, 3 (1), 54–63.
(6) International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. ICH, Impurities in New Drug Substance ICH Q3A, Eu-ropean Medicines Agency; 2006.
(7) International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. ICH, Impurities in New Drug Products ICH Q3B, Eu-ropean Medicines Agency, 2006.
(8) International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. ICH, Pharmaceutical Development ICH Q8, European Medicines Agency, 2009.
(9) International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. ICH. Stability Testing of New Drug Substances and Products Q1A (R2), European Medicines Agency, 2003.
(10) Bakshi, M.; Singh, S., Development of validated sta-bility-indicating assay methods-critical review, Journal of Pharmaceutical and Biomedical Analysis 2002, 28, 1011–1040.
(11) Rajveer, B.; Monika, O.; Agnihotri, V.; Arjun, C.; Harpalsing, G., Current trend in performance of forced degradation studies for drug substance and drug products, Journal of Drug Delivery and Thera-peutics 2020, 10, 2–s, 149–155.
(12) Blessy, M.; Patel, R. D.; Prajapati, P. N.; Agrawal, Y. K., Development of forced degradation and stability indicating studies of drugs – A review, Journal of Pharmaceutical Analysis 2014, 4 (3), 159–165.
(13) Sharma, M. K.; Murugesan, M., Forced degradation study an essential approach to develop stability indi-cating method, Journal of Chromatography Sep. Tech. 2017, 8 (1).
(14) De Alvarenga Junior, B. R.; Carneiro, R. L., Chemo-metrics approaches in forced degradation studies of Pharmaceutical drugs, Journal List Molecules 2019, 24 (20).
(15) Shah, R. P.; Kumar, V.; Singh, S., Liquid chromatog-raphy/mass spectrometric studies on Atorvastatin and its stress degradation products, Rapid communication in Mass Spectrometry 2008, 22, 613–622.
(16) Petkovska, R.; Cornett, C.; Dimitrovska, A., Develop-ment and validation of rapid resolution RP-HPLC method for simultaneous determination of Atorvas-tatin and related compounds by use of chemometrics, Analytical Letters 2008, 41, 992–1009.
(17) Gigovska, M. H.; Petkovska, A.; Acevska, J.; Nakov, N.; Manchevska, B.; Antovska, P.; Ugarkovic, S.; Di-mitrovska, A., Optimization of a forced degradation study of Atorvastatin employing an experimental de-sign approach, Macedonian Journal of Chemistry and Chemical Engineering 2018, 37, 2, 111–125.
(18) Piponski, M.; Stoimenova, T. B.; Piponska, M.; Ser-afimovska, G. T., Concepts in development of fast, simple, stability indicating HPLC method for analysis of atorvastatin related compounds in tablets, Journal of Analytical and Pharmaceutical Research 2018, 7, 4. DOI: https://doi.org/10.15406/japlr.2018.07.00265.
(19) Shulyak, N.; Piponski, M.; Kovalenko, S.; Stoimeno-va, T. B.; Balkanov, T.; El-Subbagh, H. I.; Drapak, I.; Omotosho, J. O.; Logoyda, L., Development of a nov-el, fast, simple HPLC method for determination of Atorvastatin and its impurities in tablets, Scientia Pharmaceutica, 2021, 89, 16.
(20) Vukkum, P.; Babu, J. M.; Muralikrishna, R., Stress Degradation behavior of Atorvastatin calcium and de-velopment of a suitable stability-indicating LC method for the determination of Atorvastatin, its related impu-rities, and its degradation products, Sci. Pharm. 2013, 81, 93–114.
(21) Destefano, J. J.; Schuster, S. A.; Lawhorn, J. M.; Kirk-land, J. J., Performance characteristics of new superfi-cially porous particles, Journal of Chromatography A, 2012, 1258, 76–83.
(22) Marchand, D. H.; Croes, K.; Dolan, J. W.; Snyder, L. R., Column selectivity in reversed-phase liquid chro-matography: VII. Cyanopropyl columns, Journal of Chromatography A, 2005, 1062 (1), 57–64.
(23) International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use ICH, Validation of Analytical Procedures, European Medicines Agency, 1995.
How to Cite
Copyright (c) 2022 Elena Trajchova Kovachovska, Jelena Acevska, Katerina Brezovska, Stefan Trajkovic, Ivana Mitrevska, Sonja Ugarkovic, Aneta Dimitrovska
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The authors agree to the following licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
- Share — copy and redistribute the material in any medium or format
- Adapt — remix, transform, and build upon the material
- for any purpose, even commercially.
Under the following terms:
Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- NonCommercial — You may not use the material for commercial purposes.