Pharmacokinetic Study OF Zearalenone ZEA In Weaned Pig

Studies have confirmed that Zearalenone(ZEA)is a secondary fungal metabolite produced mainly by the soil borne fungi known as Fusariumgraminearum.These soil fungi are common in temperate and warm countries,and it is a regular contaminant of cereal crops worldwide and consequently animal feeds.The chemical structure of Zearalenone sufficiently resembles 17 ?-estradiol.It works in such way that it binds to the estrogen receptor and can therefore cause disruptions in the endocrine,causing hyperestrogenism with severe infertility problems and morphological imbalance which include persistent estrus,ovarian atrophy,decreased fertility,stillbirth,etc.in reproductive organs of various mammalian species especially in swine.After ingestion and absorption,ZEAis quickly metabolized by two principal pathways:reduction to a-zearalenol and ?-zearalenol(?-ZEL?-ZEL),which can be further reduced to a-zearalanol(a-ZAL)and P-zearalanol(P-ZAL),respectively.Studies have showed that the estrogens potency of these metabolites deviates with a-ZEL showing the highest binding affinity to estrogen receptors,followed by the parent compound ZEA.It is obvious that for the investigation of the pharmacokinetics of zearalenone and its metabolites in swine plasma,the availability of sensitive and validated analytical methods is necessary.So we used high-performance liquid chromatography(HPLC)methods in combination with ultraviolet.Since it was the aim to use the method for the analysis of a high number of samples which were taken as a part of a pharmacokinetic study with Zearalenone in swine,special attention has been paid to the development of a simple,cheap and straightforward sample clean-up.In addition,it was the aim to keep the chromatographic run-time as short as possible.To clarify the pharmacokinetics and residues of Zearalnone and-its major metabolites a-zearalenol(?-ZEL)in swine,Zearalenone was then administered orally(po)to swine at a dosage of 0.1 mg/kg body weight.Blood samples were collected from the jugular veins of each animal with heparinized syringes at 10,20,30 and 40 minutes and at 1,1.5,2,3,4,6,8,10,12 and 24 hours after ZEA administration.The concentrations of ZEA,a-ZEL in the plasma were quantified using UV-HP LC.Detection limits for zearalenone was 1ng/ml,Recovery from plasma atlow ng/ml concentrations was high(80-90%).The assay utilized a single liquid-liquid extraction with ethyl acetate.We found out that our assay was linear over a concentration range from 0.5 to 200 ng/ml,the maximum plasma concentration(Cmax)of ZEA was 157.33ng/ml,(T max)was 3.68h.The area under the curve AUC 0-? was 2447.7h*?g/L,the elimination half-life t 1/2?was 17.44h,the distribution·half-life t1/2?was 2.73h,the volume of distribution Vd(area)was 10.28 L/kg,the plasma clearance Cl was 0.408L/h,the mean residence time MRT was 15.58,which belong to two compartment model.The developed assay was applied to a pharmacokinetic study after an oral dose po of zearalenone in swine.