SYNTHESIS, CHARACTERIZATION AND QUANTITATION OF REGIOISOMERIC IMPURITY IN NIMODIPINE BULK AND FORMULATION
Keywords:NI, IR, NMR, GCMS, RP-HPLC, Validation
Objective: The present research work was directed towards the synthesis characterization and quantitation of regioisomeric impurity of Nimodipine i.e. diethyl 1, 4-dihydro-2,6-dimethyl pyridine dicarboxylate in bulk and tablet formulation, by UV,IR,NMR and GC-MS techniques and a RP-HPLC method was developed as per ICH Q2B guidelines for quantitation of 1, 4-Dihydro-2, 6-Dimethyl-4-(p-nitro phenyl) pyridine-3,5 dicarboxylate (NI) from bulk and formulation.
Methods: The synthesis of NI was carried out by Hantzch pyridine synthesis, by using p-nitrobenzaldehyde, ethylacetoacetate, in presence of ammonia and methanol as a catalyst. The percentage yield was found to be 89.29%. Recrystallization and purification of NI was done. The preliminary evaluation was done on laboratory scale via melting point, elemental analysis and TLC.
Results: The melting point of impurity was found to be 156-1580C. The TLC of impurity was carried by using Chloroform: Methanol (9:1) and the Rf was found to be 0.79. The confirmation of structure of NI was carried out by using sophisticated techniques i.e., FT-IR, NMR (13C and 1H), GC-MS etc. The RP-HPLC method was developed to quantify the NI in Nimodipine bulk and formulation as per ICH Q2B guidelines. The method validation was done as per ICH guidelines.
Conclusion: The validated optimized method was found to be linear, prÃ©cised, robust, rugged and accurate. Finally NI was quantified from bulk Nimodipine and its marketed tablet formulation. It was concluded that the amount of NI, present in tablet was found to be 0.1% and in the bulk 0.067% respectively. Thus it was revealed that the NI was found to be within the limit laid down ICH guidelines (Not more than 0.1 %).
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