Advanced LC-MS/MS-Based Impurity Profiling And Forced Degradation Characterization Of Sulfamethoxazole And Clindamycin In Combined Pharmaceutical Formulations

Abstract

Background:Forced degradation and impurity profiling are essential steps in determining the stability and safety of pharmaceutical compounds. This study evaluates the degradation behaviour and impurity profiling of Sulfamethoxazole and Clindamycin under ICH-recommended stress conditions using LC-MS/MS.

Methodology:Stress degradation was performed under acidic, basic, oxidative, thermal (wet heat), and photolytic (UV) conditions. High-resolution LC-MS/MS analysis was used to identify the parent compounds and associated degradation products. Validation studies including linearity, accuracy, robustness, and ruggedness were conducted to ensure method reliability.

Results:Maximum degradation was observed under basic conditions (8.97%). Acidic, oxidative, and thermal stress also produced distinct degradation peaks. UV exposure led to unexpected assay gain (-4.66%) due to matrix concentration effects. MS/MS spectra confirmed multiple degradation products with mass accuracy <5 ppm. Validation showed linear response (R² > 0.999) across tested concentrations, high accuracy (98–102%), and robustness under varied method conditions.

Conclusion:The developed LC-MS/MS method reliably identified degradation patterns and impurity profiles of Sulfamethoxazole and Clindamycin. The method is robust, accurate, and suitable for regulatory applications, quality assurance, and impurity investigations.