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Macrolides – Monitoring in Surface Water by LC-ESI-MS/MS and In Silico Prediction of ADMET Parameters Relevant to Ecotoxicity

The aim of study was to monitor macrolides in surface water by LC-ESI-MS/MS and to predict toxic potential by ADMET PredictorTM in order to elucidate their impact on environment and health. ADMET-related descriptors (ADMET Predictor 8.1, SimulationsPlus, USA) relevant to environmental toxicity were computed using four models: the fathead minnow acute toxicity model based on lethal effects on Pimephales promelas (Minnow LC50, TOX FHM), the concentration needed to inhibit 50% growth in protozoan species Tetrahymena pyriformis (Th pyr pIGC50), the lethal concentration that results in death of 50% of Daphnia magna (water fleas) (Daphnia LC50, TOX DM) and bioconcentration factor (BCF). Erythromycin (ERY) was detected in 14 samples out of 148 (9.5%) in concentration 0.3 – 5.3 mg/L, while azithromycin (AZY) in 6 of 148 samples (4%) and concentration 0.2 – 1.1 mg/L. The results of this in silico study revealed that investigated macrolides are non-biodegradable molecules (TOX BIODEG 96%). Predicted BCF for ERY and AZY were 0.155 and 0.234, TOX DM 170.1 and 1140.503 and TOX FHM 3.948 and 12.539, respectively. Based on predicted scores for BCF, TOX DM and TOX FHM ERY has been shown as more ecotoxic substance comparing to AZY. Macrolide antibiotics were determined to potentially pose a significant risk and because of that ERY and AZY have been posted at EC Watch list. In silico studies are valuable tool in prioritizing pharmaceutical products for ecotoxicological assessments, especially for an assessment of antibiotics that cause antimicrobial resistance over long period exposure to low concentrations.

macrolides ; LC-ESI-MS/MS ; ecotoxicity ; ADMET predictor analysis

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