IDENTIFICATION AND ISOLATION OF CHLORHEXIDINE DIGLUCONATE IMPURITIES

We report the identification of 11 impurities in variously stressed ch lorhexidine digluconate (CHG) solutions. The structural assignment of each CHG impurity involved tentative identification from HPLC-MS data followed by synthesis of the appropriate standard, isolation of the im purity from the CHG solution by flash chromatography, and comparison o f HPLC-MS, HPLC-UV, and NMR data of the impurity with the standard. Si x of the synthetic impurity standards represent new compounds. Degrada tion studies of CHG solutions systematically stressed by heat, light, and low pH are reported with identification and approximate quantifica tion of resulting impurities. Degradation mechanisms were proposed for each set of stress conditions applied to CHG solutions. Parallels wer e noted between the way CHG degrades in the thermospray interface of t he HPLC-MS and the way CHG degrades with shelf time. Similarities were noted in the synthetic starting materials of CHG and the final degrad ation products.