Temperature-dependent tissue residue depletion and withdrawal time of orally administered tylosin tartrate in starry flounder, Platichthys stellatus

The purpose of this study was to demonstrate the effect of water temperature on residue depletion and withdrawal times (WTs) of tylosin in serum, muscle plus skin, liver, and kidney of the starry flounder, Platichthys stellatus , post oral (PO) administration of tylosin tartrate (TT) at 10 mg/kg dosage for 5 consecutive days. Samples were taken 3, 5, 7, 14, and 21 days post last dose, and tylosin was quantified using liquid chromatography-tandem mass spectrometer (HPLC-MS/MS). The elimination half-life ( T 1/2 ) for each tissue was calculated using ln2/ k and the WT was calculated using the WT 1.4 software at 99% statistical tolerance limit with 95% confidence. High concentrations of tylosin were detected in liver and kidney samples. A decrease in water temperature from 22 to 13 °C prolonged the T 1/2 in all the tissue samples. The T 1/2 were 1.82 and 6.19 d in serum, 2.63 and 3.92 d in muscle plus skin, 4.53 and 13.59 d in liver, and 10.83 and 28.88 d in kidney at 22 and 13 °C, respectively. The WTs for tylosin in the kidney, liver, muscle plus skin, and serum samples were in the following order: 111.7 d > 50.7 d > 20.1 d > 0 d at 22 °C and > 120 d > 81.3 d > 27.9 d > 0 d at 13 °C, respectively. Furthermore, WT (with T 1/2 ) and water temperature were negatively correlated, in all the tissue samples. Further, our results suggest a WT of 28 d for TT (marker residue; tylosin A) in the muscle plus skin tissue (target tissue) of P. stellatus for its safe consumption. Overall, our study provides a theoretical basis for the effect of water temperature on the drug residue pattern and elimination kinetics of PO administered TT in P. stellatus , which is important for improving food safety in farmed fish. • Platichthys stellatus were orally administered tylosin at 10 mg/kg for 5 days. • Lower water temperature prolonged tylosin elimination half-life in all the tissues. • Withdrawal time and water temperature negatively correlated for all the tissues. • WT of 28 d recommended for P. stellatus consumption post oral tylosin administration. • Improved understanding of tylosin residue depletion kinetics and WT determination.