Revelle L K, Doub W H, Wilson R T, Harris M H, Rutter A M
Food and Drug Administration, Division of Drug Analysis, St. Louis, Missouri 63101.
Pharm Res. 1993 Dec;10(12):1777-84. doi: 10.1023/a:1018986501194.
We report the identification of 11 impurities in variously stressed chlorhexidine 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 impurity from the CHG solution by flash chromatography, and comparison of HPLC-MS, HPLC-UV, and NMR data of the impurity with the standard. Six of the synthetic impurity standards represent new compounds. Degradation studies of CHG solutions systematically stressed by heat, light, and low pH are reported with identification and approximate quantification of resulting impurities. Degradation mechanisms were proposed for each set of stress conditions applied to CHG solutions. Parallels were noted between the way CHG degrades in the thermospray interface of the HPLC-MS and the way CHG degrades with shelf time. Similarities were noted in the synthetic starting materials of CHG and the final degradation products.
我们报告了在不同条件下受压的葡萄糖酸氯己定（CHG）溶液中11种杂质的鉴定情况。每种CHG杂质的结构确定包括：首先根据高效液相色谱-质谱（HPLC-MS）数据进行初步鉴定，然后合成相应的标准品，通过快速柱色谱法从CHG溶液中分离出杂质，并将该杂质的HPLC-MS、HPLC-紫外（UV）和核磁共振（NMR）数据与标准品进行比较。其中六种合成杂质标准品代表新化合物。本文报道了对CHG溶液分别进行加热、光照和低pH值等系统应激条件下的降解研究，包括对产生的杂质进行鉴定和大致定量。针对施加于CHG溶液的每组应激条件，提出了降解机制。注意到CHG在HPLC-MS热喷雾接口中的降解方式与CHG随储存时间的降解方式之间存在相似之处。还注意到CHG的合成起始原料与最终降解产物之间的相似性。
