Different spectrophotometric methods for simultaneous quantitation of Vericiguat and its alkaline degradation product: a comparative study with greenness profile assessment.

Investigations concerning novel drugs and their induced degradation products are necessary for clinical research and quality control in the pharmaceutical industry. Four spectrophotometric techniques have been performed for simultaneous quantitation of Vericiguat (VER) and its alkali-induced degradation product (ADP) without prior separation. Method A is a dual wavelength method (DW) that estimates the absorbance difference at 314-328 nm, and 246-262 nm for VER and ADP; respectively. Method B uses a ratio difference method (RD) to estimate the ratio spectrum's amplitude difference (DP318-342) and (DP284-292) for VER and ADP; respectively. Method C uses a first derivative ratio method (1DD) to estimate the peak ratio spectrum amplitude of the first derivative at 318 and 275 nm for VER and ADP; respectively. Method D uses the mean centering of the ratio spectra (MCR) to estimate amplitude values for VER and ADP at 337 and 292 nm; respectively. In a concentration range of 5.00-50.00 µg/mL for VER and 5.00-100.00 µg/mL for ADP, the methods were validated following ICH criteria and utilized to estimate VER in bulk and its dosage form. The methods' greenness was assessed via three tools: the green analytical procedure index (GAPI), analytical eco-scale, and analytical greenness assessment (AGREE).

The first validated stability-indicating HPLC/DAD method for quantitation of Vericiguat in its pharmaceutical formulation; Application to degradation kinetic studies.

The stability of innovative drug formulations and the development of appropriate stability-indicating methods remain major focuses of recent pharmaceutical analysis. In the present study, an efficient stability-indicating HPLC-DAD technique has been described and validated for the determination of Vericiguat (VER); a novel oral soluble guanylate cyclase (sGC) stimulator used in heart failure. VER's stability under various stress conditions was examined. It was shown that VER was sensitive to alkaline, oxidative and thermal degradation. Mass spectrometry (MS) in electrospray ionization mode was performed to figure out the structure of the alkaline and oxidative degradation products. Efficient separation of VER and its induced degradation products was accomplished using isocratic elution mode on the Inertsil ODS-C18 column. The mobile phase composed of water: acetonitrile (70:30 v/v) with 0.1% O-phosphoric acid; pH was adjusted to 2.22 and a flow rate of 0.80 mL/min. VER was detected at 332 nm over a concentration range of 2.00-20.00 µg/mL. The retention time was 4.500 ± 0.005 min and the correlation coefficient was 0.9996. Following the International Conference of Harmonization's guidelines, the analysis was validated to be specific, fast, simple, precise and accurate for utilization in routine analysis and quality control of VER in its pharmaceutical formulation. Additionally, the suggested technique was expanded to investigate the kinetics of alkaline, oxidative and dry heat degradation.