Synthesis, characterization and development of validated RP-HPLC method for the estimation of process-related impurity diethyl 4-(3-chlorophenyl)-2, 6-dimethyl-1, 4-dihydropyridine-3, 5-dicarboxylate from amlodipine bulk and formulation

Abstract

The synthesis, characterization and quantitation of process related impurity diethyl 4-(3-chlorophenyl)-2, 6-dimethyl-1, 4-dihydropyridine-3, 5-dicarboxylate from amlodipine bulk and Tablet formulations. The scheme was performed by using Hantzch pyridine synthesis. The impurity was recrystallized and preliminary evaluation was done on lab scale viz. Melting point, TLC and elemental analysis. The melting point of impurity was found to be 158-160 0 C. The TLC of impurity was carried out by using benzene: pyridine: methanol in the ratio of 5:3:2 was selected as mobile phase for quantification of impurity. The Rf value of the impurity was found to be 0.80. The conformation of synthesized Amlodipine impurity was carried out by using sophisticated instrument such as, FT-IR, NMR, GC-MS, and RP-HPLC method was developed to identify and quantify the Amlodipine impurity in bulk and formulation as per ICH Q2B guidelines. The method was found to be linear, precise, accurate, robust and rugged. Finally diethyl 4-(3-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate impurity synthesized and quantified from amlodipine bulk and Tablet formulations. Quantization of process related impurity of amlodipine in bulk and tablets was carried out. Impurity was found in bulk and in tablet I & II it was found to be 0.215%, 0.276%.and 0.323% respectively. As per the ICH limit the amount of impurity is more than 0.1% indicates that the impurity found in bulk and tablet formulations is potential impurity.