Study On The Multi-residue Determination Of The Metabolites Of Albendazole In Animal Tissues

The problems of food safety have been greatly concerned by both governments and orgnizations.The detection of prohibited drugs and the excess of leditimate drugs in food are becoming hot issues.Albendazole is an anthelmintic benzimidazole widely used as veterinary and human medicine for the treatment of infections caused by helminthes. Because albendazole and its metabolites,which constitute the marker residu,may manifest themselves posing a health hazard to consumers,many countries and European Union have set their maximum residue limits in animal edible tissues.There are no corresponding reference standards;therefore,it is necessary to research it.Two different methods(HPLC-PDA and UPLC-PDA) have been developed for the determination of the marker residu of albendazole(albendazole sulphoxide albendazole sulphone and albendazole-2-aminosulphone) in different matrix(musle,kidney,liver).The dissertation consists three parts.Chapter 1:The general situation of veterinary drug residues was reviewed.The harmfulness and the causes of veterinary drug residue were introduced.Meanwhile, sample pretreatment techniques(solid phase extraction,solid phase micro-extraction, microwave-assisted extraction,supercritical fluid extraction,gel permeation chromatography,accelerated solvent extraction,matrix solid-phase dispersion) and analytical techniques(immunoalysis,thin layer chromatography,capillary electrophoresis, high performance liquid chromatography,high performance liquid chromatography-mass spectrometry,gas chromatography,gas chromatography-mass spectrometry) were summarized.Chapter 2:The research status of albendazole and its metabolites was reviewed.A HPLC-PDA method for the determination of the marker residu of albendazole has been developed.The metabolites were separated well in 10.5 minutes when a gradient method was used.With acetonitrile/25mM mixed phosphate as mobile phase(pH=6.86) and C₁₈ as an analytical column,the sample pretreatment conditions were optimized.Acetonitrile was chosen as the extracting solution,n-hexane and MCX solid phase extraction cartridges were used for the purification.Finally the eluant was blowed by nitrogen to proximal dry.The reliability of the method was verified.The recoveries of the metabolites were obtained by various samples,which range from 79.1 to 89.4%.The relative standard deviations were in the range 3.41～9.45%for spiked samples.The limits of quantitation were 0.015mg/kg.Chapter 3:An UPLC-PDA method for the determination of the marker residu of albendazole has been developed.The metabolites were separated well in 2.5 minutes when a gradient method was used.With acetonitrile/10mM(pH=6.86) mixed phosphate as mobile phase and C₁₈ as an analytical column,the sample pretreatment conditions were optimized.Acetonitrile was chosen as the extracting solution,n-hexane and MCX solid phase extraction cartridges were used for the purification.Finally the eluant was blowed by nitrogen to proximal dry.The reliability of the method was verified.The recoveries of the metabolites were obtained by various samples,which range from 78.1 to 88.8%.The relative standard deviations were in the range 3.35～9.36%for spiked samples. The limits of quantitation were 0.003mg/kg.