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Determination of Possible Potential Genotoxic Impurities in Lenalidomide Drug Substance by Simple RP-HPLC Method
Corresponding Author(s) : Kishore Gaddam
Asian Journal of Chemistry,
Vol. 32 No. 12 (2020): Vol 32 Issue 12, 2020
Abstract
This study is concerned with development and validation of HPLC method for the simultaneous detection and quantification of methyl 2-(chloromethyl)-3-nitrobenzoate (MCN), methyl 2-(bromomethyl)-5-nitrobenzoate (MMM), methyl 2-(bromomethyl)-6-nitrobenzoate (MON), methyl 2-(bromomethyl)-4-nitrobenzoate (MPN) and 2-methyl-3-nitrobenzoic acid methyl ester (MNM), which are the genotoxic impurities of lenalidomide. Chromatographic separation was accomplished using a Waters HPLC system equipped with Ascentis Express F5 (150 × 4.6 mm, 2.7 μm) using mobile phase composed of solvent A (0.1% perchloric acid): solvent B (methanol 80% and acetonitrile 20%); 55:45, vol/vol. The selected impurities were detected using UV detector set at 210 nm. The standard curves showed linearity in the range of concentrations 4.59-91.2 ppm (for MCN), 6.58-90.0 ppm (for MMM), 3.96-89.1 ppm (for MON), 6.47-89.7 ppm (for MPN) and 4.28-90.1 ppm (for MNM). The statistical results of method precision, system precision, specificity, accuracy, ruggedness was found to be within limits of acceptance. All the impurities were stable in lenalidomide test samples up to 24 h.
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- N. Tageja, Anticancer. Agents Med. Chem., 11, 315 (2011); https://doi.org/10.2174/187152011795347487
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- Y.Y. Syed and L.J. Scott, Drugs, 73, 1183 (2013); https://doi.org/10.1007/s40265-013-0071-x
- C.A. Dasanu and D.T. Alexandrescu, Eur. J. Haematol., 82, 231 (2009); https://doi.org/10.1111/j.1600-0609.2008.01176.x
- M.H. Dogu, I. Sari, S. Hacioglu and A. Keskin, North. Clin. Istanb., 1, 191 (2015); https://doi.org/10.14744/nci.2014.36036
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- ICH Harmonisation for Better Health, 2014 (2014).
- Guidance for Industry Q3A (R2), Impurities in New Drug Substances, in: International Conference on Harmonization (2006).
- Guidance for Industry Q3B (R2), Impurities in New Drug Products, in: International Conference on Harmonization (2006).
- U.S. Department of Health and Human Services, Food and Drug Administration (FDA), Genotoxic and Carcinogenic Impurities in Drug Substances and Products. Rockville, MD (2008).
- S.S. Prasad, G.V.K. Mohan and A.N. Babu, Orient. J. Chem., 35, 140 (2019); https://doi.org/10.13005/ojc/350115
- S. Swetha, B.M. Ishaq, H.A. Ahad and V. Prakash, Indo-Am. J. Pharm. Sci., 2, 1173 (2015).
- L.M. Reddy, K.J. Reddy, L.B. Reddy and P.R. Reddy, E-J. Chem., 9, 1165 (2012); https://doi.org/10.1155/2012/673736
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References
N. Tageja, Anticancer. Agents Med. Chem., 11, 315 (2011); https://doi.org/10.2174/187152011795347487
S.A. Holstein, V.J. Suman and P.L. McCarthy, Ther. Adv. Hematol., 9, 175 (2018); https://doi.org/10.1177/2040620718775629
C. Fang, D. Zhu, H. Dong, M. Ji, J. Wu, X. Xu, G. Cheng, C. Wu and J. Jiang, Int. J. Clin. Exp. Med., 8, 10705 (2015).
Y.Y. Syed and L.J. Scott, Drugs, 73, 1183 (2013); https://doi.org/10.1007/s40265-013-0071-x
C.A. Dasanu and D.T. Alexandrescu, Eur. J. Haematol., 82, 231 (2009); https://doi.org/10.1111/j.1600-0609.2008.01176.x
M.H. Dogu, I. Sari, S. Hacioglu and A. Keskin, North. Clin. Istanb., 1, 191 (2015); https://doi.org/10.14744/nci.2014.36036
Ed Price. Identifying Impurities in APIs, Seqens, Accessed on May 2020, Available at: https://www.pcisynthesis.com/identifying-impurities-in-apis/.
ICH Harmonisation for Better Health, 2014 (2014).
Guidance for Industry Q3A (R2), Impurities in New Drug Substances, in: International Conference on Harmonization (2006).
Guidance for Industry Q3B (R2), Impurities in New Drug Products, in: International Conference on Harmonization (2006).
U.S. Department of Health and Human Services, Food and Drug Administration (FDA), Genotoxic and Carcinogenic Impurities in Drug Substances and Products. Rockville, MD (2008).
S.S. Prasad, G.V.K. Mohan and A.N. Babu, Orient. J. Chem., 35, 140 (2019); https://doi.org/10.13005/ojc/350115
S. Swetha, B.M. Ishaq, H.A. Ahad and V. Prakash, Indo-Am. J. Pharm. Sci., 2, 1173 (2015).
L.M. Reddy, K.J. Reddy, L.B. Reddy and P.R. Reddy, E-J. Chem., 9, 1165 (2012); https://doi.org/10.1155/2012/673736
S.A. Siadati, M. Payab and A. Beheshti S.A. Siadati, Chem. Rev. Lett., 3, 61 (2020).
N.Z. Alzoman, J. Chromatogr. Sci., 54, 730 (2016); https://doi.org/10.1093/chromsci/bmv247
ICH Expert Working Group. Assessment and control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk, M7 (R1) (2017).
ICH Expert Working Group. Validation of Analytical Procedures: Text and Methodology, Q2 (R1) (2005).