Assessment of environmental impact of a novel stability-indicating RP-HPLC method and reported methods for the determination of selexipag in bulk and dosage form: A comparative study using different greenness assessment tools

Abstract

Selexipag is a novel non prostanoid prostacyclin receptor agonist used to treat pulmonary arterial hypertension. Novel RP-HPLC method was developed and validated for analyzing the cited drug in presence of its impurities namely; ACT-333679 and ACT-609440, respectively. The separation was achieved on INERTSIL ODS C18 column (5 μm, 100 × 4.6 mm) using a mobile phase consisting of methanol: 20 mmoles phosphate buffer (pH 4, adjusted using o- phosphoric acid) (20:80, v/v) at a flow rate of 1 ml/min and UV detection was carried out at 270 nm. The method was linear over concentration range (100–600 μg/ml) with regression coefficient 0.999. By preparing selexipag and its impurities in laboratory-prepared mixtures, the suggested method's selectivity was verified. In accordance with the International Conference on Harmonization (ICH) guidelines, the procedure was fully validated. The suggested method worked well for determining selexipag in both bulk and medicinal dosage form. No significant difference between the published method and the current method was found, according to statistical analysis. The newly developed method's green profile assessment was carried out and compared with previously reported chromatographic methods using four greenness assessment tools. AGREE (the most recent developed greenness assessment tool) and ESA (the most applicable tool) were applied for the comparative study. Upon comparison, the proposed method recorded the highest AGREE and ESA scores among the compared methods. The developed method was found to be simple, accurate and eco-friendly method making it suitable for the routine analysis of selexipag in dosage form in quality control laboratories.