Stability-Indicating Spectrofluorimetric Methods for the Determination of Metolazone and Xipamide in Their Tablets. Application to Content Uniformity Testing

摘要

A highly sensitive, simple and rapid stabilityindicating spectrofluorimetric method was developed for the determination of metolazone (MET) and xipamide (XPM) in their tablets. The proposed method is based on the measurement of the native fluorescence ofMET in methanol at 437 nm after excitation at 238 nm and XPM in alkaline methanolic solution at 400 nm after excitation at 255 nm. The fluorescence- concentration plots were rectilinear over the range of 2.0- 20.0 ng/mL for MET and 0.2- 2.0 μg/mL for XPM, with lower detection limits (LOD) of 0.35 ng/mL and 0.02 μg/mL and a lower quantification limit (LOQ) of 1.05 ng/mL and 0.07 μg/mL forMETand XPM, respectively. Themethodwas successfully applied to the analysis of MET and XPM in their commercial tablets and the results were in good agreement with those obtained using the official and comparison methods, respectively. Furthermore, content uniformity testing of the studied pharmaceutical tablets was also conducted. The application of the proposed method was extended to stability studies of MET and XPM after exposure to different forced degradation conditions, such as acidic, alkaline, oxidative and photolytic degradation conditions, according to ICH Guidelines. Moreover, the method was utilized to investigate the kinetics of the alkaline, acidic and photolytic degradation of MET. The apparent first-order rate constants and half-life times were calculated. Proposals for the degradation pathways for both MET and XPM were postulated.