SPECTROSCOPIC AND VOLUMETRIC TECHNIQUES FOR THE ESTIMATION OF IVABRADINE IMPURITY 3,3'-(PROPANE-1,3-DIYL)BIS(7,8-DIMETHOXY-1,3,4,5-TETRAHYDRO-2H-BENZO[D]AZEPIN-2-ONE)

Objective: Two simple and sensitive techniques - one spectrophotometric and one titrimetric- have been developed for the determination of 3,3'-(propane-1,3-diyl)bis(7,8-dimethoxy-1,3,4,5-tetrahydro-2H-benzo[d]azepin-2-one) commonly known as ivabradine impurity-9 (IVA-9). Methods: The spectrophotometric method is based on the oxidation of drug impurity by excess cerium (IV) sulphate in acidic medium and the subsequent reaction of the remaining Ce(IV) with a known amount of ferrous ammonium sulphate. The resultant ferric ion is then made to react with thiocyanate in acid medium to form a brown coloured complex which is analyzed spectrophotometrically against the reagent blank. In the volumetric method, the un-reacted Ce(IV) is titrated against standard ferrous ammonium sulphate to estimate the quantity of IVA-9. Results: The colored complex showed an absorption maximum at 479 nm when measured  spectrophotometrically. The stated methods are validated statistically using the International Council for Harmonization guidelines-ICH Q2(R1) for precision and accuracy. The method showed a linear response from 0.5 to 100µg/ml with a correlation coefficient of 0.9985 Conclusion : No estimation techniques have been reported to date for the determination of this molecule. The proposed techniques may be used for the routine quantification in its pure form and also in presence of its parent drug molecule Ivabradine.