Synthesis and establishment of Amlodipine impurity G reference standard

Abstract

Dimethyl-4-(2-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate which is impurity of amlodipine besilate was synthesized. Hantzsch condensation of methyl acetoacetate with 2-chlorobenzadehyde in 2-propanol at heated under reflux temperature at 85 °C for about 10 hours yielded the yellow powder. This product was purified by column chromatography and the structure was identified by spectroscopic methods (IR, MS, NMR), that was characterized amlodipine impurity G (dimethyl -4-(2-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate). The quality of the impurity was determined by high performance liquid chromatography HPLC method and validated by guideline of The International Conference on Harmonization 2003 Then this impurity was determined homogeneity and assigned value to establish reference standard as Appendix 3 of World Health Organization (WHO technical series 943, 2006) and Statistical methods for use in proficiency testing by inter-laboratory comparison, International Organization for Standardization (ISO 13528), 2005.