title: Residue study of doxycycline and 4-epidoxycycline in pigs medicated via-drinking water.
abstract: A study was performed to determine the residues in edible tissues of healthy pigs after continuous administration of doxycycline with drinking water for five consecutive days at a dose rate of 10.5 mg doxycycline kg-1 body weight (BW) per day. Quantitation was performed using a validated HPLC method with fluorescence detection. The method was able to separate doxycycline and its 4-epimer, 4-epidoxycycline. This epimer was found in kidney, liver, skin, fat and muscle tissue. The method was validated at the maximum residue limit (MRL), at half the MRL and at double the MRL for both doxycycline and 4-epidoxycycline. Linear calibration curves were obtained in spiked tissues (r > 0.99). The accuracy of the calibrators of the calibration curves was within -20% to +10%. The accuracy and precision (expressed as the within-run repeatability) were found to be within the required ranges for the specific concentration. The limits of detection and limits of quantification were below one-half of the MRL. The quantification limits were 50 micrograms kg-1 for doxycycline and 100 micrograms kg-1 for 4-epidoxycycline in kidney and liver, 20 micrograms kg-1 for doxycycline and 50 micrograms kg-1 for 4-epidoxycycline in skin and fat and 10 micrograms kg-1 for doxycycline and 50 micrograms kg-1 for 4-epidoxycycline in muscle tissue. The withdrawal time was calculated according to the recommendations of the European Agency for the Evaluation of Medicinal Products (EMEA/CVMP/036/95) and was set at 3 days. The plasma concentration of doxycycline and the stability of doxycycline in drinking water were also determined during the treatment period. The mean plasma concentration of doxycycline during the treatment period ranged from 0.83 to 0.96 microgram ml-1. Thirty-six hours after the withdrawal from medicated drinking water, no plasma levels could be detected. Samples of medicated water were taken at time zero and at 24 h after addition of doxycycline to the drinking water. No statistically significant difference in the mean drinking water concentration was seen at time zero and at time 24 h (Student's t-test, alpha = 0.05).
authors.affiliation: Department of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Gent, Merelbeke, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Croubels
authors.forename: K
authors.initials: K
authors.lastname: Baert
authors.forename: J
authors.initials: J
authors.lastname: De Busser
authors.forename: P
authors.initials: P
authors.lastname: De Backer
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000032:analysis* / Q000097:blood; D004318:Doxycycline / Q000032:analysis* / Q000097:blood; D004350:Drug Residues / Q000032:analysis*; D005260:Female; D005506:Food Contamination / Q000032:analysis*; D006801:Humans; D008297:Male; D008460:Meat; D013552:Swine; D013997:Time Factors; D019155:Veterinary Drugs / Q000032:analysis* / Q000097:blood; D014867:Water
chemical_list: D000900:Anti-Bacterial Agents; D019155:Veterinary Drugs; D014867:Water; D004318:Doxycycline