Determination of flumequine and 7-hydroxyflumequine in plasma of sheep by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method for the simultaneous determination of flumequine and its metabolite 7-hydroxyflumequine in sheep plasma was described. The two compounds were extracted from 100 microl of plasma by liquid-liquid extraction. Aliquots (100 microl) were injected onto the HPLC system and separated on a LiChrospher Select B column with an isocratic system. The compounds were detected by fluorimetric detection for concentrations below 500 microg/l and by UV detection for the concentrations exceeding 500 microg/l. The range of the validated concentrations were 50000 to 5 microg/l and 500 to 10 microg/l with mean recovery rates of 87+/-3% and 60+/-1% for flumequine and 7-hydroxyflumequine, respectively.

Determination of residues of flumequine and 7-hydroxyflumequine in edible sheep tissues by liquid chromatography with fluorimetric and ultraviolet detection.

A simple, sensitive, and rapid method for simultaneous determination of residues of flumequine and its microbiologically active metabolite 7-hydroxyflumequine in 100 mg sheep edible tissues (muscle, liver, kidney, and fat) by liquid chromatography is reported. After liquid-liquid cleanup with ethyl acetate, tissue extracts were injected onto a Select B column. The 2 compounds were determined by ultraviolet and fluorimetric detection. The method was repeatable and reproducible for flumequine and 7-hydroxyflumequine in muscle, liver, kidney, and fat, with limits of detection below 2 and 3 micrograms/kg for flumequine and 7-hydroxyflumequine, respectively. Mean recoveries for flumequine were 90 +/- 7, 82 +/- 7, 89 +/- 5, and 82 +/- 6% in muscle, liver, kidney, and fat respectively. Mean recoveries for 7-hydroxyflumequine were 91 +/- 2, 90 +/- 4, 86 +/- 3, and 84 +/- 4% in muscle, liver, kidney, and fat, respectively.

Pharmacokinetics of flumequine in sheep after intravenous and intramuscular administration: bioavailability and tissue residue studies.

The pharmacokinetic properties of flumequine and its metabolite 7-hydroxyflumequine were determined in six healthy sheep after single intramuscular (i.m.) and intravenous (i.v) injections at a dose of 6 mg/kg body weight. The tissue residues were determined in 20 healthy sheep after repeated i.m. administration with a first dose of 12 mg/kg and nine doses of 6 mg/kg. The flumequine formulation used was Flumiquil 3% Suspension Injectable. The mean plasma concentrations of flumequine after i.v. administration were described by a three-compartment open model with a rapid distribution and a relatively slow elimination phase. The low value of volume of distribution at steady state (Vdss) (0.52 +/- 0.24 L/kg) and high value of volume of distribution (Vdlambda3) (5.05 +/- 3.47 L/kg) emphasized the existence of a small compartment with a slow rate of return to the central compartment. The mean elimination half-life was 11.5 h. The 7-hydroxyflumequine plasma levels represented 2.3% of the total area under the curve. The mean plasma concentrations of flumequine after i.m. administration were characteristic of a two-compartment model with a first order absorption. The mean maximal plasma concentration (1.83 +/- 1.15 microg/mL) was obtained rapidly, i.e. 1.39 +/- 0.71 h after the i.m. administration. The fraction of dose absorbed from the injection site was 85.00 +/- 30.13%. The minimal concentrations of flumequine during repeated treatment were significantly lower in females than in males. Eighteen hours after the last repeated i.m. administration, the highest concentration of flumequine was observed at the injection sites followed by kidney, liver, muscle and fat. The highest concentration of 7-hydroxyflumequine was observed in the kidney and was ten times lower than the flumequine concentration. The longest flumequine elimination half-life was observed in the fat.