Clavulanic acid is commonly used in combination with penicillin and cephalosporin antibiotics to overcome bacterial resistance. Clavulanic acid is produced and isolated from Streptomyces clavuligeru with ethyl acetate and then converted to a stable form. One secondary purification approach uses nonaqueous precipitation of potassium clavulanate by adding the potassium salt of 2-ethylhexanoic acid in isopropanol to the primary isolation extract. While 2-ethylhexanoic acid is soluble in the organic solvent, a small fraction may co-precipitate with the potassium clavulanate.
The United States Pharmacopeia (USP) monograph for potassium clavulanate describes a GC–FID method to determine 2-ethylhexanoic acid in the active pharmaceutical ingredient (API). This contribution describes a simpler approach for determining 2-ethylhexanoic acid in clavulanate with a Reagent-Free Ion Chromatography (RFIC) system. USP clavulanate reference standards were prepared at a 150-fold lower concentration in deionized water than the current USP method, spiked with 2-ethylhexanoic acid, and injected directly without additional sample pretreatment. The target analyte was separated from clavulanate-related peaks using electrolytically generated potassium hydroxide eluent and measured by suppressed conductivity detection.
ExperimentalAnalyses are performed using a Dionex ICS-2100, AS Autosampler and Chromeleon Chromatography Workstation. Separations use an IonPac AG11/AS11 column set (USP L61) with electrolytically generated KOH eluent.1
Results and Discussion
1. Dionex Corporation. Determination of 2-Ethylhexanoic Acid Impurity in Clavulanate Using a Reagent-Free Ion Chromatography System. Application Note 262 (LPN 2608, Oct., 2010); Sunnyvale, California, USA
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