Efonidipine HCl Ethanolate is an antihypertensive drug with 1, 4 dihydropyridine and phosphinane derivative. Forced degradation study was performed in Efonidipine as per the guidelines by ICH Q1A (R2). Extensive degradation was observed in alkaline condition, slight degradation was observed in photolytic condition while acidic, oxidative, thermal condition didnt show any degradation. Degradation products were separated on Thermo Hypersil BDS C18 column (250 X 4.6 mm, 5µ), mobile phase in gradient mode using ammonium acetate buffer and acetonitrile with detection at wavelength of 254 nm. Six degradation products in alkaline and four degradation products in photolytic condition were identified by HPLC and characterized by mass spectrometry using LC-Q-TOF-MS and degradation pathway was proposed. This is the typical case of degradation where co-solvent methanol reacts with Efonidipine to form pseudo degradation products - DP1, DP4, DP5 and DP6 respectively. Three degradation products DP1, DP3 and DP4 in alkaline condition were isolated by preparative HPLC and were characterized by LC-Q-TOF-MS, 1H/13C NMR and IR techniques. By characterization with these techniques, DP1 is characterized as 3-2-(N-benzylanilino)ethyl 3-oxo-2,2-dimethylpropyl hydrogen 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl) pyridin-3-yl-3-phosphonate, DP3 is characterized as 2-(N-benzyl-N-phenylamino) ethanol, DP4 is characterized as 3-methoxy-2,2-dimethylpropyl hydrogen 1,4-dihydro-2,6-dimethyl-5-methyloxycarbonyl-4-(3-nitro)phenylpyridin-3-yl-3-phosphonate.The developed method was validated as per guidelines by ICH with respect to linearity, accuracy, precision, limit of detection and robustness.
Key words: Forced degradation, Efonidipine, Preparative HPLC, LC-Q-TOF-MS, NMR and IR