Low Level Determination of Genotoxic Impurity in Deferasirox Formulation

Pravish Kumar Tiwari, Padmakar Sathe, Navin Devadiga

Department of Chemistry, Ramnarian Ruia College, Mumbai, India..

DOI: 10.4236/jasmi.2013.34023                

Abstract

4-hydrazinobenzoic acid has been highlighted as one of the potential genotoxic impurities (PGIs). A sensitive HPLC method was developed and validated for the determination of 4-hydrazino benzoic acid in Deferasirox Tablet. HPLC method on Zorbax SB C18 column (250 × 4.6 mm i.d.), 5 μm, with UV Detector was used. The proposed method was cost effective, specific, linear, accurate, rugged and precise. The calibration curves showed good linearity over the concentration range of 0.5 μg/ml to 1.5 μg/ml with respect to the sample. The correlation coefficient was 0.999. Excellent recoveries of 102% were obtained at the level 0.5 μg/ml.

Keywords

Deferasirox; Genotoxic; 4-Hydrazinobenzoic Acid; HPLC

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	S. Glowienke, W. Frieauff, T. Allmendinger, H. Martus, W. Suter and L. Mueller, “Structure-Activity Considerations and in Vitro Approaches to Assess the Genotoxicity of 19 Methane-, Benzen and Toluenesulfonic Acid Esters,” Mutation Research/Genetic Toxicology and Environmental Mutagenesis, Vol. 581, No. 1-2, 2005, pp. 23-24. http://dx.doi.org/10.1016/j.mrgentox.2004.10.004
[2]	“Guidelines on the Limits of Genotoxic Impurities CPMP/ SWP/ 5199/02,” The European Medicines Agency [EMEA], Committee for Medical Products for Human Use [CHMP].
[3]	I. Colon and S. M. Richoll, “Determination of Methyl and Ethyl Esters of Methanesulfonic, Benzenesulfonic and P-Toluenesulfonic Acids in Active Pharmaceutical Ingredients by Solid-Phase Microextraction (SPME) Coupled to GC/SIM-MS,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 39, No. 3-4, 2005, pp. 477-485. http://dx.doi.org/10.1016/j.jpba.2005.04.037
[4]	H. G. Ramjit, M. M. Singh and A. B. Coddington, “Gas Chromatographic/Mass Spectrometric Analysis of Methyl Methanesulphonate and Ethyl Methanesulphonate in the Bismesylate Salt of DPI 201-106, a Positive Inotropic Agent for the Treatment of Heart Failure,” Journal of Mass Spectrometry, Vol. 31, No. 8, 1996, pp. 867-872. http://dx.doi.org/10.1002/(SICI)1096-9888(199608)31:8<867::AID-JMS362>3.0.CO;2-Q
[5]	S. Harikrishna, K. Nagabhusana Reddy, Y. Suresh, M. Ramkrishna, M. Sarat, K. Kishore and C. Rambabu, “Low-level Determination of 4-Hydrazino BenzoicAcid in Drug Substance by High Performance Liquid Chromatography/Mass Spectrometry,” E-Journal of Chemistry, Vol. 7, No. 2, 2010, pp. 403-408. http://dx.doi.org/10.1155/2010/616494
[6]	S. Steinhauser, U. Heinz, M. Bartholoma, T. Weyhermüller, H. Nick and K. Hegetschweiler, “Complex Formation of ICL670 and Related Ligands with FeIII and FeII,” European Journal of Inorganic Chemistry, Vol. 2004, No. 21, 2004, pp. 4177-4192. http://dx.doi.org/10.1002/ejic.200400363