Tissue residue depletion kinetics and withdrawal time estimation of doxycycline in grass carp, Ctenopharyngodon idella, following multiple oral administrations.

This study aimed to determine the plasma and tissue residue depletion kinetics of doxycycline (DC) in grass carp (Ctenopharyngodon idella) after daily oral administrations at 20 mg/kg for 3 days, and to calculate the corresponding withdrawal times. Following drug administrations, samples of plasma, liver, kidney, gill and muscle + skin were collected at predetermined time points (0.25, 0.5, 1, 3, 5, 7, 14, 21, 28, 35, 42, 49 and 56 days) and analyzed for concentrations of DC using a LC-MS/MS method. The results showed that liver had the highest concentrations and the slowest depletion compared to other tissues, with detectable DC up to 49 days (58.9 ± 12.8 μg/kg). The WT 1.4 software and "reschem" package were used to calculate withdrawal times, and the results were similar. The results suggest a withdrawal time of 41 days for Europe and China and 50 days for Japan is needed for DC in grass carp after 3 daily oral administrations at 20 mg/kg. Overall, this study improves our understanding of the tissue residue depletion kinetics of DC in fish, and the results may help regulatory agencies to determine proper withdrawal periods based on different regulatory standards in different countries to ensure safety of aquatic food products.