Astri Rogstad

Pharmacokinetics and bioavailability of flumequine and oxolinic acid after various routes of administration to Atlantic salmon in seawater

Abstract The present preclinical study was performed to investigate the pharmacokinetics of flumequine in Atlantic salmon (Salmo salar L.) in seawater after administration of different doses and dosage formulations. Flumequine was administered intravenously (dose 4.9 mg/kg fish) and orally from the drug delivery system Aqualets as Apoquin 5 g/kg (dose 25 mg/kg) and 10 g/kg (dose 50 mg/kg), respectively. Experiments were carried out with oxolinic acid administered in the same way for the purpose of comparing the two compounds. The seawater temperature was 5±0.2°C in all experiments. The pharmacokinetic calculations showed that the distribution half-life for flumequine was t 1 2 α = 1.3 h and for oxolinic acid t 1 2 α = 0.7 h . The drugs were absorbed rapidly, and flumequine reached a plasma concentration of Cmax = 2.26 μg/ml after a single oral dose of 25 mg/kg, whereas oxolinic acid reached Cmax = 0.99 μg/ml. The apparent bioavailability of flumequine was found to be 40–45%, whereas the apparent bioavailability of oxolinic acid varied from 25% at a dose of 50 mg to 40% at a dose of 25 mg/kg body weight of fish. The distribution profile of flumequine in the various compartment of fish appeared to be different from that of oxolinic acid. After a single oral dose (25 mg/kg) the areas under the concentration-time curves showed that flumequine was 2.3 times more concentrated in plasma and 2.6 times more concentrated in liver compared to oxolinic acid. In muscle the difference was less pronounced, flumequine being 1.4 times more concentrated than oxolinic acid.

Pharmacokinetic study of oxytetracycline in fish. I. Absorption, distribution and accumulation in rainbow trout in freshwater

Abstract The absorption, distribution and elimination of oxytetracycline in plasma, muscle, liver, intestine, mucus, skin and vertebrae in rainbow trout in freshwater were studied after a single dose of 150 mg/kg fish. The absorption of the drug was slow and only about 2.6% of the administered dose was absorbed at the time of maximum absorption. The distribution to all tissues of the fish was good, and a considerable affinity of OTC to tissues was observed. The slow elimination was demonstrated by the long halflife which was 11.6 days from plasma.

Optimization of Solid Phase Extraction of Oxytetracycline from Fish Tissue and its Determination by HPLC

Abstract The extraction of oxytetracycline from fish tissues by use of solid phase extraction columns has been studied. The best recovery was obtained by using a C8 column and eluting with water/acetone (5% and 10% mixtures). The sensitivity of the method was 5 ng/g for muscle and 10 ng/g for liver. The repeatability of the assay on 10 samples at 1 μg/g and 0.1 μg/g was determined by the standard deviation equal to 4.2% and 6.7%, respectively. The recovery was 89.3% and 94.8%, respectively. The recovery of the internal standard (demeclocycline) was 82.8%.

Rapid Assay for Monitoring Residues of Enrofloxacin and Sarafloxacin in Fish Tissues by High Performance Liquid Chromatography

Abstract A simple and rapid method for extraction and HPLC-analysis of residues of enrofloxa-cin and sarafloxacin in muscle and liver from Atlantic salmon is presented. After homogenization of the tissue the fat was separated by extraction into organic solvents and the aqueous phase was analysed on the chromatograph. The method is selective and robust. The sensitivity is 5 ng/g for enrofloxacin and 10 ng/g for sarafloxacin. The method was validated and correlated with a more sensitive, but time-consuming pretreatment procedure for monitoring enrofloxacin. The method is also applicable for monitoring residues of the drugs oxolinic acid and flumequine, respectively, in Atlantic salmon.

Optimization of sample cleanup procedure for determination of diarrhetic shellfish poisoning toxins by use of experimental design

In routine monitoring of diarrhoeic shellfish poison (dinophysistoxin-1 and okadaic acid) there appeared to be an inconsistency between the mouse bioassay and existing chemical analysis based on liquid chromatography. The sample cleanup procedure has been subject to minor modifications in an effort to overcome the problem. However, further studies have appeared necessary and in this study all experimental factors that can influence the sample cleanup using solid-phase extraction columns prior to the LC analysis have been evaluated by use of experimental statistical design in order to understand the effect of the various factors and to optimize the conditions for recovery of the toxins. Based on our experiments we suggest using a solid-phase extraction silica column of 100 mg in the sample cleanup procedure and washing solvents composed of dichloromethane instead of chloroform to minimize the effect of stabilizing alcohol. It is sufficient to apply 7.5 ml hexane-dichloromethane (1:1) to the column in the first washing step and 2.5 ml of dichloromethane in the final washing. Elution is complete by use of 2.5 ml chloroform with 3.5% methanol. Toxic shellfish tested by this procedure confirmed the mouse bioassay.

Simultaneous determination of sulphadiazine and trimethoprim in plasma and tissues of cultured fish for residual and pharmacokinetic studies

Clean-up and high-performance liquid chromatographic methods for the simultaneous determination of sulphadiazine and trimethoprim in fish plasma and tissues have been developed. The average recovery of sulphadiazine varied from 74% in liver to 92% in plasma, whereas that of trimethoprim varied from 60% in liver to 97% in plasma. The sample pretreatment procedures were simple, selective and robust, having a limit of quantification of 250 ng/ml for trimethoprim and 50 ng/ml for sulphadiazine in plasma, 15 ng/g for sulphadiazine and 80 ng/g for trimethoprim in muscle, and 30 ng/g for sulphadiazine and 160 ng/g for trimethoprim in liver. The assay was tested on plasma from Atlantic salmon treated with Tribrissen.

Extraction and high performance liquid chromatographic determination of enrofloxacin in fish serum and tissues

Abstract The extraction of enrofloxacin from fish serum and tissues using solid phase extraction columns has been studied. Good recoveries were obtained by using C2 columns for cleanup of serum and C18 columns for clean-up of tissue samples. the sample pretreatment procedures are selective and robust having a sensitivity of 1 ng/ml and 1 ng/g from serum and tissues, respectively, making them particularly useful for monitoring drug residue levels. the recoveries were 97–100% from serum and 96–99% from tissues. the method was tested on fish treated with enrofloxacin.

A gas chromatographic method for testing antioxidants

Abstract and SummaryA gas chromatographic method for evaluating the effect of antioxidants is described. Emulsions of linoleic acid both with and without antioxidant are oxidized enzymatically. Concentrations of uncreacted linoleic acid are measured at varying incubation times and various concentrations of both lipoxidase and antioxidant. Two antioxidants have been tested. The method is simple, precise, and reproducible. The inhibition mechanism and experimental conditions are discussed.

Assay for dinoflagellate toxins in mussels by gas chromatography and principal components analysis

Abstract The profile of organic components in tissue from the posterior adductor muscle of blue mussels, Mytilus edulis , was chemometrically determined. After methanolysis of the tissue and silylation, the components were separated by gas chromatography and the normalized, scaled peak-height data for 22 peaks were subjected to principal components treatment. Mussels from a population shown by the mouse bioassay to contain paralytic shellfish poison were examined. The profile from their tissues differed from that of mussels from the same population after depuration of toxicity for four weeks in water free of toxic dinoflagellates.

Evaluation of antioxidant activity: II. application of a heme- Catalyzed system

A study was made of the inhibitory effect of the antioxidants propyl gallate,tert-butylated hydroxyanisol, α-tocopherol and ethoxyquin on the hemoglobin-catalyzed oxygenation of linoleic acid. The concentration of unchanged fatty acid after varying incubation periods and at varying concentrations of antioxidant was measured by gas chromatography. The effect of the antioxidants is compared with results obtained previously from the lipoxygenase-catalyzed oxidation of a linoleic acid emulsion. It is concluded that all 4 antioxidants are good inhibitors of fatty acid oxidation cata-lyzed by hemoglobin.