Utilization of N-bromosuccinimide for the sensitive spectrophotometric determination of pipazethate HCl as antitussive drug in pure and dosage forms

Abstract

Objectives: Three simple, sensitive, precise, reproducible and validated spectrophotometric methods have been developed for the quantification of pipazethate HCl as antitussive drug in pure and dosage forms.

Methods: The methods are based on utilization of N-bromosuccinimide as an oxidant and three dyes, amaranth, methylene blue, and indigo carmine, as auxiliary reagents. The proposed methods are based on oxidation reaction of pipazethate HCl with a known excess of N-bromosuccinimide in acid medium, followed by determination of unreacted N-bromosuccinimide by the reaction with a fixed amount of dyes, amaranth, methylene blue, and indigo carmine followed by the measurement of the absorbance at 520, 663 and 610nm, respectively. The optimization of the reaction conditions was investigated.

Results: Under the optimum conditions, linear relationships with good correlation coefficients (0.9998-0.9999) were found over the concentration ranges of 0.3-9.0, 0.5-12 and 0.5-10μgmL^-1 with a limit of detection (LOD) of 0.1, 0.15 and 0.15μgmL^-1 using amaranth, methylene blue, and indigo carmine methods, respectively. Intra-day and inter-day accuracy and precision of the methods have been evaluated. No interference was observed from the common tablet excipients.

Conclusion: The developed methods were validated in accordance with ICH guidelines and successfully applied to the analysis of pipazethate HCl in dosage forms with good accuracy and precision. The reliability of the methods was further ascertained by performing recovery studies via the standard addition method. Statistical comparison of the results obtained by applying the proposed methods with those of the reported method by applying Student's t-test and variance ratio F-test at the 95% confidence level revealed good agreement and indicates no significant difference in accuracy and precision.

Keywords: Chlorhydrate de pipazéthate; Dosage forms; Formes posologiques; Method validation; N-bromosuccinimide; Pipazethate hydrochloride; Spectrophotometry; Spectrophotométrie; Validation de la méthode.