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)

Abstract

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.

Research progress on the impurities identification and determination in pharmaceuticals

“…Such as Evaporative Light Scattering Detector (ELSD), 66 Charged Aerosol Detector (CAD), 67 Refractive Index (RI), 68 Chemical Lumines-cent Nitrogenspecific Detector (CLND). 69 Although the quantitative capabilities of these are strong, their qualitative capabilities are weak, especially for the direct qualitative determination of unknown substances, which requires the use of known reference materials or related chromatographic qualitative reference data (retention time) for qualitative identification. This also highlights the advantages of Mass Spectrometer (MS) and Nuclear Magnetic Resonance spectrometer (NMR) in impurity qualitative analysis.…”

Computational and spectral studies of 3,3'-(propane-1,3-diyl)bis(7,8-dimethoxy-1,3,4,5-tetrahydro-2H-benzo[d]azepin-2-one)

“…1a & 1b). The spectroscopic and volumetric estimation of the title molecule has been studied recently by the same authors [16]. At times, the exploratory studies of such molecules lead to the development of alternate drug molecules with better pharmacodynamics or help us to assess its toxicity impact.…”