ABSTRACT
The objective of this study was to establish a withdrawal period for flunixin in milk by quantifying 5-hydroxyflunixin, the marker residue, in bovine milk as a function of time, following intravenous treatment of lactating dairy cows with flunixin-N-methyl glucamine (Banamine or Finadyne). Lactating dairy cows were dosed on three consecutive days at 2.2 mg of flunixin free acid/kg of body weight/day. Milk was collected twice daily and assayed using a liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) procedure. The method was validated at concentrations in the range 0.5-250 ppb. The concentrations for 5-hydroxyflunixin measured 12 h after the last administration of drug ranged from 1.56 to 40.6 ppb for all cows. Milk concentrations for 5-hydroxyflunixin were used to establish withdrawal periods of 36 h using guidelines established by the U.S. Food and Drug Administration/Center for Veterinary Medicine and 24 h using guidelines established by the European Medicinal Evaluation Agency/Committee on Veterinary Medicinal Products.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Cattle/metabolism , Clonixin/analogs & derivatives , Clonixin/administration & dosage , Clonixin/pharmacokinetics , Milk/chemistry , Animals , Chromatography, Liquid , Drug Residues/analysis , Female , Kinetics , Lactation , Mass Spectrometry , Time FactorsABSTRACT
Two complementary methods for identifying and measuring sulfonamide residues in eggs were developed for use in surveying eggs for potential drug residues. The first method uses liquid chromatography-tandem mass spectrometry (LC-MS-MS) to confirm the presence of sulfonamide residues in eggs. During its validation the limit of confirmation was estimated to be 5-10 ng/g (ppb) depending on the drug. Also, a method for measuring residue level by liquid chromatography with ultraviolet detection (LC-UV) was validated using the same extraction procedure as the confirmatory method. The determinative method was validated over the 50-200 ppb range. Samples were prepared by homogenizing whole egg, extracting with acetonitrile, and cleaning up with a C(18) solid-phase extraction cartridge. For confirmation, analytes were separated by gradient LC on a C(18) column, ionized by electrospray ionization (ESI), and detected by MS-MS with an ion trap mass spectrometer. For determination, analytes were separated by a different gradient LC procedure and detected by UV at 287 nm. Fifteen drugs were dosed individually in laying hens, and residues of parent drug and/or metabolites were found in eggs for all the drugs. Validation was based on repetitive analyses of control samples, control samples fortified at 100 ppb sulfonamides, and samples of blended incurred eggs.
Subject(s)
Chromatography, Liquid/methods , Drug Residues/analysis , Eggs/analysis , Mass Spectrometry/methods , Spectrophotometry, Ultraviolet/methods , Sulfonamides/analysis , Animals , Chickens , Female , Reference Standards , Reproducibility of ResultsABSTRACT
Plasma and skin concentrations of orbifloxacin (Orbax tablets, Schering-Plough Animal Health) were assessed in 14 clinically normal dogs and 14 dogs with pyoderma following oral administration of the drug at 7.5 mg/kg once daily for 5 to 7 days. Skin biopsies and whole blood samples were obtained before dosing and at the time of the expected maximum concentration in skin (3 hours after dosing) on the first and on the fifth to seventh day of dosing. Skin biopsies and plasma were analyzed for orbifloxacin concentrations by high-performance liquid chromatography. Dogs with pyoderma had significantly higher mean skin concentrations of orbifloxacin within 3 hours of administration (Day 0: 7.80 +/- 3.40 mcg/g, Days 4 to 6: 9.47 +/- 6.23 mcg/g) than did dogs with normal skin (Day 0: 3.85 +/- 1.08 mcg/g, Days 4 to 6: 5.43 +/- 1.02 mcg/g). After dosing on Day 0 and after five to seven daily treatments, dogs with pyoderma had significantly higher mean orbifloxacin skin:plasma ratios (1.40 and 1.44, respectively) than did clinically normal dogs (0.81 and 0.96, respectively). The accumulation of orbifloxacin in diseased skin may contribute to the efficacy of this compound for the treatment of bacterial skin infections.