A Review on Impurity Profiling, Degradation Studies, and Bio-Analytical Method of Anti-Fungal Drugs

Antifungal drugs play a vital role in combating life-threatening fungal infections, yet their therapeutic effectiveness and safety critically depend on purity, stability, and reliable analytical assessment. This review comprehensively discusses impurity profiling, forced degradation studies, and bioanalytical method development of key antifungal agents within a single integrated framework - an approach not previously consolidated in the literature. The review covers major antifungal classes including azoles, polyenes, allylamines, and pyrimidine analogues. It summarizes impurity types - organic, inorganic, and residual solvents - as classified by ICH guidelines, along with their origins, formation mechanisms, and control strategies. Advanced chromatographic and spectroscopic techniques such as HPLC, LC-MS/MS, and GC-MS are highlighted for impurity detection. Forced degradation studies under ICH-recommended stress conditions are evaluated for drugs including flucytosine, terbinafine, tolnaftate, benzoic acid, and azoles. Recent advances in bioanalytical method validation using LC-MS/MS and UPLC-MS/MS for pharmacokinetic and bioequivalence studies are also outlined. The review underscores the importance of these analytical strategies in ensuring safety, efficacy, and quality control of antifungal formulations - from raw material characterization to finished product evaluation - in alignment with international pharmacopeial and ICH standards.