Development And Application Of Veterinary Drug Quinocetone Metabonomics Technology In Chicken

As the fast development of economy, animal derived food is becoming more and more important in our life, but veterinary drugs residues in every kind of animal derived food has become a hot topic of public health. The veterinary drugs residues are the veterinary drugs or its metabolites of in the cells, tissues or organ of animals. The veterinary drugs residues not only prevent the development of the cultivation economy, but also harm the people's health. To improve the development of economy and to defend the people's health, it is essential to research the mechanisms of veterinary drugs in the body of animals and to pose possible drug consumption and drug holiday to reduce veterinary residual.Quinocetone is a new veterinary drug, which was synthesized by Lanzhou Institute of Animal and Veterinary Pharmaceutics Sciences, Chinese Academy of Agricultural Sciences. The experiment of drug action proved Quinocetone can effectively improve the growth and feed efficiency of food animals. To follow the prohibition of the use of carbadox (CBX) and olaquindox (OLA) which are the well known members of the quinoxaline-1, 4-dioxide family, Quinocetone will be used more extensively. At present, the documents have reported the research of pharmacology, toxicology, residual detection, and drug holiday of quinocetone, but there hasn't been the report of the study of mechanisms and metabonomics of quincetone residuals.Metabonomics is a new technique that simultaneously measures all metabolites which is ignored in the past and determines the synthetic characteristic of biological specimen. To apply metabonomics technology, from the metabolic fingerprint and profile the people can procure utmost message of biological specimen, discover the new metabolism signal (or residual signal), illuminate formation mechanism of the new metabolism signal (or residual signal), and establish original residual exosyndrome technique and analytical method to provide new method of resid research.In this study, using the metabonomics technique, the change of exogenous metabolin and endogenous metabolin in the body of chicken which took orally quincetone was studied. The residual mechanisms of QTN and its metabolites in the body of animal were revealed.In order to study the residual mechanisms of QTN, the chicken plasma, liver and muscle sample of the administration group which took orally quincetone and the control group were gathered. Firstly, using liquid chromatography coupled to tandem mass spectrometry, the metabolism of quincetone in the chicken's body was studied, and the two metabolites, DMO-QTN and DDI-QTN, was found and validated. Subsequently, the parameters of liquid chromatography and tandem mass spectrometry were optimized. To follow, the metabonimics techniques platform was established, which consisted of the method of quantitative analysis of exogenous veterinary drugs and its metabolites and qualitative analysis of endogenous metabolin and the method of pattern recognition the spectra of LC-MS.On the base of the above research, using the established metabonomics technique platform, the dose-time-response relationship of QTN was studied. The result of dose-response was found that the residue level of QTN and its metabolites increased to accompany the dosage of QTN in the plasma and liver, but after four hours there was not the residual of QTN and its metabolites in chicken muscle, in addition, the endogenous metabolin in chicken plasma, liver and muscle from different dose group could be distinguished. The result of time-response revealed that the residue level of QTN and its metabolites was not accumulated to follow the time of administration of QTN in chicken plasma and liver, after four hours there was not any residual of QTN and its metabolites in the chicken muscle, in addition, the endogenous metabolin in chicken plasma, liver and muscle from different dose group could be distinguished.Based on the results of this study, following conclusions could be made: (1) The platform of metabonomics technique for veterinary residual study was successfully established. Using metabonomics technique the metabolism phaenotype of administration group and control group could be distinguished readily. It was also proved that metabonomics technique could be applied to the study of veterinary drugs residual. (2) Using metabonomics analysis, the change of dose-response or time-response of exogenous metabolin and the diversity of the endogenous metabolin phaenotype could be distinguished.