A Critical Review of Chromatographic Techniques for Impurity Profiling and Stability-Indicating Analysis of Ceftriaxone Sodium.

Abstract

Objective: This review critically evaluates chromatographic methodologies for impurity profiling and stability-indicating analysis of ceftriaxone sodium, with particular focus on polymerized impurities that pose significant patient safety concerns.Significance: Ceftriaxone sodium, a widely prescribed third-generation cephalosporin, exhibits broad-spectrum antibacterial activity and convenient once-daily dosing. However, impurities-particularly polymerized forms-pose safety risks such as hypersensitivity and anaphylaxis. In contrast to earlier review focused on drug determination, this work emphasizes impurity profiling and highlights gaps in current analytical practice.

Methods: A systematic literature survey was conducted across official pharmacopoeias and major databases (ScienceDirect, Scopus, PubMed, Google Scholar) using keywords: ceftriaxone sodium, impurity profile, polymerized impurities, ceftriaxone stability, and ceftriaxone degradation.

Results: Reversed-phase HPLC with C18 columns was the predominant technique (93%), most commonly coupled with UV detection at 254 nm. Isocratic elution was applied in 82% of methods, with acetonitrile as the preferred organic modifier; ion-pairing agents were used in 39% of cases, and 20 µL was the most commonly used injection volume (54%). Only 14% of studies addressed polymerized impurities, with the Chinese Pharmacopoeia uniquely mandating gel filtration chromatography for their assessment.

Discussion: Current impurity profiling strategies have limitations in detecting polymerized forms due to their low abundance, variable polymerization degrees, poor stability, and interference from co-existing molecules.

Conclusions: There is an urgent need for robust, sensitive, and polymer-specific analytical approaches to improve impurity profiling, and safeguard patient safety. Future studies should incorporate greenness (AGREE), risk (RAPI), and analytical performance (BAGI) metrics to identify sustainable and reliable strategies for ceftriaxone impurity assessment.