The use of biomimetic chromatography to predict acute aquatic toxicity of pharmaceutical compounds

Abstract The potential of biomimetic chromatography to predict ecotoxicological endpoints of pharmaceutical compounds was investigated. For this purpose, a data set of previously and newly measured chromatographic retention data for 36 structurally diverse drugs was used. Standardized retention times were measured on the immobilized artificial membrane, human serum albumin, and alpha-1-acid glycoprotein stationary phases. As ecotoxicological endpoints, half-maximal lethal concentration values of fish and half-maximal effective concentration (immobilization) values of a water flea (Daphnia magna spp.) determined with a two-day static method were considered. Ecotoxicity values correlated with octanol-water partitioning and the positive charge of compounds contributed even more to the toxicity. Models based on membrane partition exhibited the best statistics and predictive performance, attributed to lipophilicity and membrane electrostatic interactions. Alpha-1-acid glycoprotein binding led to satisfactory models, owing to its function as a binder of neutral and basic lipophilic compounds. Albumin binding, however, did not result in sound models, as it is governed by lipophilicity and the negative charge of compounds, contrary to the mechanism of toxicity. Both membrane and alpha-1-acid glycoprotein models were superior statistically from those derived from the octanol-water system. Overall, membrane and alpha-1-acid glycoprotein retention can be suggested as promising indices to assess the ecotoxicological risk of drugs. Graphical Abstract