[Toxic impurities in chlorhexidine digluconate]

Three preparations of chlorhexidine-digluconate were analysed for contamination with a newly developed high-pressure liquid chromatographic method. Of special interest was p-chloroaniline, a toxic as well as a carcinogenic compound. We found concentrations from 1.7 to 8.5 mmol p-chloroaniline per mol chlorhexidine-digluconate, i.e. five-fold differences in the different products. Besides p-chloroaniline many other contaminating substances were found, amongst others p-chlorophenyl-isocyanate and p-chlorophenyl-carbodiimide. The least contamination was found in a branded article, and the highest degree of contamination in a "no-name"-product. During a storage period of half a year in dark glass bottles in a solution of 0.2% under various light and temperature values the p-chloroaniline concentrations increased linearly with the period of storage, with the exception of storage in the dark at 5 degrees C. A constant temperature of 35 degrees C in the dark caused a greater increase than storing at 20-25 degrees C in the dark or the light or in direct sunlight. Therefore under similar conditions it is mostly warmth which causes an increase in toxic compounds.