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Current Pharmaceutical Analysis

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ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

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Research Article

Degradation Kinetics Study of Anastrozole in Different Conditions by Reverse-Phase High-Performance Liquid Chromatography and Confirmation of its Major Degradation Product by Ultra-Performance Liquid Chromatography with Tandem Mass Spectrometry

Author(s): Linjia Sun, Xiaoyang Sun, Yu Chen, Binjie Wang and Xiaohui Chen*

Volume 15, Issue 3, 2019

Page: [217 - 223] Pages: 7

DOI: 10.2174/1573412914666180406130108

Price: $65

Abstract

Background: Drug stability is essential in the process of drug production, storage, appliance, and so on. Some drugs’ degradation products may even have a toxic side effect, which can result in safety risks and economic losses. Therefore, it is very imperative to develop a suitable stability indicating an analytical method for anastrozole which could be used for stability testing, routine and in-process quality control analysis or other further studies.

Methods: A reverse-phase high-performance liquid chromatography method was developed and validated for the degradation kinetics study of anastrozole, a selective non-steroid third-generation aromatase inhibitor, which would provide a basis for further studies on anastrozole. The degradation product was confirmed by ultra-performance liquid chromatography with tandem mass spectrometry.

Results: Results showed that the degradation behavior of anastrozole followed first-order kinetics in different temperatures, pH values and oxidation conditions. It was suggested that the degradation behavior of anastrozole was pH-dependent and it’s more stable at lower pH values.

Conclusion: A high performance liquid chromatography method was established and used to determine the residual concentration of anastrozole in this study. It was found that the degradation behavior of anastrozole followed first-order kinetics at different temperatures, pH values and oxidation conditions. According to the results, the degradation of anastrozole was found to be pH-dependent and it is more unstable in alkaline conditions. The information of degradation kinetics will be useful for understanding the chemical stability of anastrozole and provide a reference for the further preparation research and clinical therapy of anastrozole.

Keywords: Anastrozole, degradation kinetics, kinetic parameters, first-order plot degradation, RP-HPLC, drug stability.

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[1]
Goss, P.E.; Ingle, J.N.; Martino, S.; Robert, N.J.; Muss, H.B.; Piccart, M.J.; Castiglione, M.; Tu, D.; Shepherd, L.E.; Pritchard, K.I. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: Updated findings from NCIC CTG MA.17. J. Nat. Cancer Inst., 2005, 97(17), 1262.
[2]
Smith, I.E.; Dowsett, M. Aromatase inhibitors in breast cancer. N. Engl. J. Med., 2004, 2(2), 149-150.
[3]
Nagaraj, G.; Ma, C. Revisiting the estrogen receptor pathway and its role in endocrine therapy for postmenopausal women with estrogen receptor-positive metastatic breast cancer. Breast Cancer Res. Treat., 2015, 150(2), 231-242.
[4]
Davies, E.L. Breast cancer. Medicine , 2016, 44(1), 42-46.
[5]
Cuzick, J.; Sestak, I.; Baum, M.; Buzdar, A.; Howell, A.; Dowsett, M.; Forbes, J.F. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lanc Oncol., 2010, 11(12), 1135-1141.
[6]
Howell, A.; Cuzick, J.; Baum, M.; Buzdar, A.; Dowsett, M.; Forbes, J.F.; Hoctin-Boes, G.; Houghton, J.; Locker, G.Y.; Tobias, J.S. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lanc., 2005, 365(9453), 60-62.
[7]
Hiriyanna, S.G.; Basavaiah, K. Isolation and characterization of process related impurities in anastrozole active pharmaceutical ingredient. J. Braz. Chem. Soc., 2008, 19, 307-404.
[8]
Saravanan, G.; Suryanarayana, M.V.; Jadhav, M.J.; Ravikumar, N. A stress stability behavior and development of an lc assay method for anastrozole. Chromatographia, 2007, 66, 435-438.
[9]
Li, R.; Wang, F.; Chen, L.; Zhu, S.; Wu, L.; Jiang, S.; Xu, Q.; Zhu, D. Stability of an anti-stroke peptide: driving forces and kinetics in chemical degradation. Int. J. Pharm., 2014, 472(1-2), 148-155.
[10]
Zhang, Q.; Guan, J.; Rong, R.; Zhao, Y.; Yu, Z. Study on degradation kinetics of 2-(2-hydroxypropanamido) benzoic acid in aqueous solutions and identification of its major degradation product by UHPLC/TOF-MS/MS. J. Pharmaceut. Biomed. Anal., 2015, 112, 1-7.
[11]
Reddy, Y.R. Nandan, S.R.; Bharathi, D.V.; Nagaraju, B.; Reddy, S.S.; Ravindranath, L.K.; Rao, V.S. LC and LC-MS/MS study of forced decomposition behavior of anastrozole and establishment of validated stability-indicating analytical method for impurities estimation in low dose anastrozole tablets. J. Pharm. Biomed. Anal., 2009, 50(3), 397-404.
[12]
Reddy, Y.R. Ich, Validation Of Analytical Procedures: Text And Methodology; Q2(R1) 2005.
[13]
Sanming, L. Physical Chemistry; People's Medical Publishing House, 2012.
[14]
Sitaram, C.; Rupakula, R.; Reddy, B.N. Determination and characterization of degradation products of anastrozole by LC-MS/MS and NMR spectroscopy. J. Pharmaceut. Biomed. Anal., 2011, 56(5), 962-968.
[15]
Zhao, L-S.; Li, Q.; Liu, Z-Z.; Su, J.; Chen, Z-H.; Bi, K-S. Degradation kinetics of cefuroxime lysine in aqueous solution by LC-MS. Curr. Pharm. Anal., 2012, 8, 409-414.

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