Unveiling cloperastine fendizoate degradation using MS/MS: A novel HPLC method for simultaneous analysis with parabens and degradant characterization

Abstract

Environmental considerations are gaining a worthy role in the effective evaluation of analytical approaches. The purpose of this work is useful for developing and validating a novel green HPLC technique to measure Cloperastine fendizoate (CLOP), and paraben, simultaneously via existence of CLOP degradation products. CLOP is a centrally acting antitussive with antihistaminic properties, generally used for cough relieving. To construct the proposed method is through a C 18 column using a mobile phase, that includes ethanol and 0.1% orthophosphoric acid (pH= 4) at 50:50 v/v ratio, with flow rate equal to 1.0 mL/min. UV detection was employed at 250.0 nm. This method was successfully applied for the analysis of CLOP suspension formulation (Notussil®), confirming its determination. CLOP showed degradation of 22.86% under basic, 20.68% under acidic, and 12.86% under oxidative conditions after 45 minutes. MS/MS analysis obtained a major degradant with an m/z of 105.03, corresponding to benzaldehyde formed via ether bond cleavage under all stress conditions. The current method was fully validated through ICH guidelines, Demonstrating a concentration range of 5.0–200.0 µg/mL as a good linearity and 1.6 µg/mL as a limit of detection. A mean percentage recovery of 100.43 ± 0.148% was calculated to confirm the method accuracy. Through comparing the existing method, no significant differences were detected. CLOP degradation under various stress conditions was studied to highlight the importance of stability testing, while the proposed method offers environmental benefits through reduced hazardous chemicals, energy, and waste. This was further proved by quantitative evaluation using AGREE and WAC tools, which showed the method’s high greenness score and maintained performance across analytical, environmental, and practical criteria.