Development of a reversed-phase HPLC method for determination of related impurities of Lenalidomide

Document Type : Research Article

Authors

1 Department of Chemistry, Qaemshahr Branch, Islamic Azad University, Qaemshahr, Iran

2 R&D Department, Quality Control Laboratories, Tofigh Daru Research and Engineering Company, Tehran, Iran

3 Department of Chemistry, Payame Noor University, Tehran, Iran

Abstract

In this project, we have developed a reversed phase liquid chromatography method for separation and determination of lenalidomide (LENA) and related substances by using C-8 (250×4.6 mm ID, 5 μm) HPCL column. The mobile phases A and B were phosphate buffer at Ph=3.30, and (methanol:acetonitrile)(1:5 V/V), respectively. The column oven temperature was 25°C, the wavelength was 220nm, and the injection volume was 20 µl. The degradation studies using basic, acidic, oxidation, and thermal stress, were performed. In addition, in the basic stress, a significant degradation for LENA, was observed.
Also, the results showed that the resolutions of the peaks for fresh, acid stress, and thermal stress were considerably high. For example, in the case of thermal shock, the resolution of each peak to the next, was 3.6, 3.2, 5.3, and 4.7. Thus, it indicates that the method is suitable at least in view of separation and resolution for the peaks produced by thermal shock.

Graphical Abstract

Development of a reversed-phase HPLC method for determination of related impurities of Lenalidomide

Keywords


[1] .Lu, F. Payvandi, L. Wu, L. Zhang, R.J. Hariri, H. Man, R.S. Chen, The anti-cancer drug lenalidomide inhibits angiogenesis and metastasis via multiple inhibitory effects on endothelial cell function in normoxic and hypoxic conditions, Microvas. Res., 77 (2009) 78-86.
[2] E. Balaian, C. Schuster, C. Schönefeldt, U. Germing, D. Haase, S.Tuve, R. Ordemann, Selective expansion of regulatory T cells during lenalidomide treatment of myelodysplastic syndrome with isolated deletion 5q, Ann. Hematol., 95 (2016) 1805-1810.
[3] a) Ch. Grondal, M. Jeanty, D. Enders, Organocatalytic cascade reactions as a new tool in total synthesis, Nature
chem., 2, 3 (2010) 167. b) M. Bakherad, A. Keivanloo, M. Siavashi, M. Omidian, Three-component synthesis of imidazo [1, 2-c] pyrimidines using silica sulfuric acid (SSA), Chin. Chem. Lett. 25 (2014) 149-151; c) M. Bakherad, A. Keivanloo, M. Omidian, S. Samangooei, Synthesis of pyrrolo [2, 3-b] pyrazines through Sonogashira coupling reaction of 5, 6-dichloropyrazine-2, 3-dicarbonitrile with hydrazine, phenylacetylene and various aldehydes, J Chem. Res. 38 (2014) 762-764.
[4] H. Sarma, T. Jahan, H.K. Sharma, Progress in Drug and Formulation Development for the Chemoprevention of Oral Squamous Cell Carcinoma: A Review, Recent Pat. Drug Deliv. Formul., 13 (2019) 16-36.
[5] S. Görög, Critical review of reports on impurity and degradation product profiling in the last decade, TrAC Trends Anal. Chem., 101 (2018) 2-16.
[6] B.G. Yilmaz, B. Nazik, K. Kucukoglu, GC-MS Determination of MexiletineAfter Derivatization with N-Methyl-N-(Trimethylsilyl) Trifluoroacetamide in Pharmaceutical Formulatios and Comparison with HPLC Method, Pharm. Chem. J., 51 (2017) 516-521.
[7] A.G. Osman, S. Haider, A.G. Chittiboyina, I.A. Khan, Utility of alkaloids as chemical and biomarkers for quality, efficacy, and safety assessment of botanical ingredients, Phytomedicine 54 (2019) 347-356.
[8] G.B.M. Saravanan, M. Rao, M.V. Ravikumar, N. Suryanarayana, P.V.R. Someswararao, P. Acharyulu. Development of an HPLC assay method for lenalidomide, Chromatographia 66 (2007) 287-290.
[9] N.S. Raghu, Y.R. Reddy, V. Naresh, V.S. Rao, L. K. Ravindranath, Degradation Studies of Highly Potent and Life Threatening Human Birth Defect Drug—Lenalidomide by HPLC and LC-MS, J Liq. Chromatogr. Relat. Technol., 33 (2010) 654-679.
[10] L.M. Reddy, K.J. Reddy, K.L.B. Reddy, P.R. Reddy, Development of a rapid and sensitive HPLC assay method for lenalidomide capsules and its related substances, J Chem., 9 (2012) 1165-1174.
[11] N.Z. Alzoman, A validated stability-indicating and stereoselective HPLC method for the determination of lenalidomide enantiomers in bulk form and capsules, J chromatogr. Sci., 54 (2016) 730-735.
[12] S.S. Prasad, G.V.K. Mohan, A.N. Babu, Development and Validation of Stability-Indicating RP-HPLC Method for the Estimation of Lenalidomide and its Impurities in Oral Solid Dosage form, Orient. J. Chem., 35 (2019) 140-149.
[13] A. Aristizábal, G. Perilla, J.A. Lara-Borrero, R. Diez, KrCl and XeCl excilamps and LP-Hg lamp for UV and UV/H2O2 decolourization of dyes in water, Environ. technol., 41 (2020) 238-250.‏