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IMPURITY PROFILING, STRUCTURAL REACTIVITY AND STABILITY CHALLENGES OF FOSFOMYCIN: A CRITICAL REVIEW WITH EMPHASIS ON EPOXIDE INTEGRITY AS A QUALITY DETERMINANT

Authors: Pooja Deshpande; Dinesh Dantkale; Mahesh Mali; Santosh Rawool; Sharad Rode;

IMPURITY PROFILING, STRUCTURAL REACTIVITY AND STABILITY CHALLENGES OF FOSFOMYCIN: A CRITICAL REVIEW WITH EMPHASIS ON EPOXIDE INTEGRITY AS A QUALITY DETERMINANT

Abstract

Fosfomycin is a structurally unique phosphonic acid antibiotic widely used for the treatment of urinary tract infections (UTIs), particularly those caused by multidrug-resistant (MDR) pathogens. Unlike conventional β-lactam or glycopeptide antibiotics, fosfomycin exerts bactericidal action through irreversible inhibition of MurA enzyme ((UDP-N-acetylglucosamine enolpyruvyl transferase) via its strained epoxide ring. While its small molecular size and high aqueous solubility offer formulation advantages, the molecule’s inherent chemical reactivity presents significant stability and impurity-related challenges. The integrity of the epoxide moiety is directly linked to therapeutic activity, making impurity profiling a critical quality attribute (CQA).

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