Column chromatography USED in purification of genotoxic impurity sample of imatinib mesylate substance

The article describes a simple method for purifying N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidineamine for further use as a standard for quantitative determination of genotoxic impurities substance imatinib mesylate. Experimentally proved choice of sorbent used for purification of N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidineamine. The advantage of column chromatography on neutral alumina prior to crystallization methods presented in the literature. Comparative chromatographic and spectral characteristics of N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidineamine before and after purification. NMR spectroscopy evaluated quantitative content of the target substance in the purified sample.

N-(5-амино-2-метилфенил)-4-(3-пиридил)-2-пиримидинамин, иматиниба мезилат, генотоксичная примесь, колоночная хроматография, нейтральный оксид алюминия, ВЭЖХ, спектроскопия ЯМР, N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidinamine, imatinib mesylate, genotoxic impurity, column chromatography, neutral alumina, HPLC, NMR spectroscopy

1. Mashkovsky MD. Medicines. 16th ed. Moscow; 2012 (in Russian).

2. Patent WO-2008/112722 A2 (2008). Available from: http://goo.gl/NV9vVa.

3. Patent WO-2011/070588 Al (2011). Available from: http://goo.gl/9mniW1.

4. Patent WO-2004/099187 A1 (2004); Available from: http://goo.gl/IJIv4m.

5. Bhatt V, Prasad G, Bhatt H, Sharma A. Quantification of potential genotoxic impurity in imatinib mesylate by LC-MS/MS. Acta Chim Pharm Indica 2013; 3(2): 182–91.

6. Madireddy V, Babu SK, Narayanareddy P. Stability-indicative, validated, fast HPLC method for quantification of two genotoxic impurities in imatinib mesylate. Global J of Analit Chem. 2011; 2(5): 198–207.

7. Guideline on the limits of genotoxic impurities, CPMP/SWP/5199/02, EMEA/CHMP/QWP/251344/2006. London; 2006. Available from: http://goo.gl/CaQzef.

8. Lutseva AI, Bokovikova TN, Stronova LA, Agapkina MV, Bunyatyan ND. The relevance of development of a unified approach to standardization of imatinib. Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo primeneniya 2014; (3): 9–12 (in Russian).

9. Crouch R, Russell D. Easy, Precise and Accurate Quantitative NMR Application note. Agilent Technologies Inc., USA; 2011. Available from: http://goo.gl/6is1lW.

10. Kuzmina NE, Moiseev SV, Krylov VI, Yashkir VA, Merkulov VA. Possibilities of NMR spectrometry in determining trace components of mixtures. Zhurnal analiticheskoy himii 2014; 69(11): 1052–60 (in Russian).