摘要
药物残留问题一直受到人们的关注与重视。食品基体复杂，而残留物质含量极微，这就要求研究建立从复杂的基体中分离、分析并准确定量确证痕量残留的检测手段。本论文从食品中重要痕量残留入手，建立了基于色谱与色谱/质谱联用技术的分离、分析痕量残留物的方法并用于实际样品检测中，同时研制了基体标准物质以保证检测结果准确。本论文共分6章。第一章对食品中残留现状、分析技术与发展进行了概述，重点综述了本文研究对象噻嗪类染料、β－兴奋剂类药物、生物农药等药物残留的分析技术以及用于残留分析检测质量控制的基体标准物质研究进展；第二章研究了噻嗪类染料亚甲基蓝及代谢物残留分析技术，建立了液相色谱、液相色谱/串联质谱以及毛细管电泳/质谱法三种分析方法。其中液相色谱/串联质谱定量限可达0.5μg/kg；平均加标回收率为80%～91%，相对标准偏差为6.38%～9.41%。第三章建立了乳品中溴布特罗、塞曼特罗、克伦特罗、克伦潘特、羟甲基氨克伦特罗、苯氧丙酚胺、马布特罗、莱克多巴胺、利托君、沙丁胺醇、特布他林、氯丙那林和妥布特罗等13种β-兴奋剂类药物残留量的高通量液相色谱/串联质谱检测方法，并进行了实验室内与实验室间验证。检测限达0.01～0.16μg/L，添加水平为0.05～2.5μg/L时，回收率为82.5－101%。第四章针对几种主要生物农药残留进行研究。建立了茶叶中阿维菌素、甲氨基阿维菌素、乙酰氨基阿维菌素、伊维菌素、多拉菌素和莫西丁克等6种微生物源生物农药残留检测方法，对绿茶、红茶、普洱茶进行了验证，莫西丁克在5、10、20μg/kg,其余分析物在2、5、10μg/kg加标水平的平均回收率为61.7%～85.4%,相对标准偏差为9.37%～17.19%。第五章建立了水产品中鱼藤酮、印棟素、苦参碱、氧化苦参碱等4种植物源生物农药残留的检测方法，基本消除了基体干扰，平均回收率与相对标准偏差分别为88.6～95.7%和7.58～10.15%，对4种分析物的检测限为0.29～1.4μg/kg。第六章研制含有呋喃唑酮代谢物3-氨基-2-唑酮（AOZ）的鳗鲡基体标准物质。由于食品基体本身固有的易变化的特性使得单纯采用传统的纯化学物质标准品来校准检测体系难以满足要求，需要采用基体标准物质进行过程控制。本文对含有呋喃唑酮代谢物3-氨基-2-唑酮的鳗鲡基体标准物质的制备进行了研究，探讨了样品的自然污染方式、制备过程及保存形式，研制成的产品均匀、稳定，经过11家实验室协同定值，已作为国家标准物质（GBW（E）100180）发布，也是我国首个发布的兽药代谢物残留标准物质。
In the recent years, drug and pesticide residues in food have become a frequently recurringphenomenon, which requires a series of useful methods for the separation and determination oftrace residues in food matrix. In this thesis, several methods are established based onchromatography and gas chromatography/mass spectrometry for separation and analysis oftrace residues of the method and the actual samples used for detection, while the standardsubstrate material was developed to ensure the accuracy of test results. There are six partsincluded in this thesis. The first part is a review of the progress in the analysis of residues infood, focus on the analysis of thiazide dye residues, β-agonist resiudes and biopesticideresidues. In addition, the progress of matrix reference materials for pesticide and drug residuesanalysis is reviewed in the paper. In the second part, a high performance liquidchromatographic method, a high performance liquid chromatographic/tamdem massspectrometry method and a capillary electrophoresis/electrospray ionization mass spectrometryhas been developed for the determination of dye methylene blue and its metabolites in aquaticproducts, and applied to incurred samples. For HPLC-MS/MS method, the average recoveriesand the relative standard deviation ranged from80%to91%and6.38%to9.41%, respectively,and the limits of detection of4analytes were to0.5μg/kg. In the third part, an ultra-highperformance liquid chromatography method for the confirmation of multi-residues ofbrombuterol, cimaterol, clenbuterol, clenpenterol, clorprenaline, hydroxymethylclenbuterol,isoxsuprine, mabuterol, ractopamine, ritodrine, salbutamol, terbutaline and tulobuterol in milkis reported. The detection limits (CCα) and detection capabilities (CCβ) of the13analytes werefound in the range of0.01–0.16μg/L and0.03–0.21μg/L, respectively. Recoveries of thecompounds were found from82.5%to101%at the spiked level of0.05–2.5μg/L, and therelative standard deviation was within the range of7.17%and16.4%. Furthermore, aninter-laboratory study among eight laboratories was conducted to further validate the method,and the results were found satisfactory. In the fourth part, a simple and rapid analytical methodfor the simultaneous determination of abamectin, emamectin, eprinomectin,I vermectin,doramectin and moxidectin residues in tea by ultra-performance liquid chromatography-electrospray tandem mass spectrometry（UPLC/ESI-MS/MS） has been developed. Thismethod is validated for the determination of avermectin residues in various tea samples,including green tea, black tea and Puer tea. The average recoveries and the relative standard deviations ranged from61.7%to85.4%and from9.37%to17.19%, respectively. In the fifthpart, a method for determining residues of4botanical insecticides oxymatrine, matrine,rotenone and azadirachtin in fish by liquid chromatography-electrospray tandem massspectrometry is described. The average recoveries and the relative standard deviation rangedfrom88.6-95.7%and7.58-10.15%, respectively, in spiked fish samples at concentration levelsg/kg for oxymatrine, matrine and rotenone, and from2to ranging from0.5to10g/kg. Thelimits of detection (LOD) for4oxymatrine, matrine, rotenone and50azadirachtin were0.29,0.37,0.21and1.4μg/kg. The method is accurate, specific and sensitive for the analysis ofoxymatrine, matrine, rotenone and azadirachtin in fish samples. In the sixth part, amethodology for preparing and certifying the reference material of3-amino-2-oxazolidinone ineel muscle lyophilisates was presented. Furazolidone was accessed to eel by dipping fish inpond with furazolidone solution at a dosage of ca0.16mg/L. With the metabolism offurazolidone in eel,the muscles contain a certain concentration of AOZ as furazolidonemetabolite was obtained. Lyophilization of the muscles was performed in one batch and400bags of samples were obtained by the procedure of homogenation, cryodesiccation andirradiation. The homogeneity and stability of the sample was examined. The value of thechemical constituent of the sample was certified through the collaborative analysis programparticipated by11laboratories using isotope dilution liquid chromatography-tandem massspectrometry,and the uncertainty assessment was performed. The reference materials have beenapproved as certified reference materials in2009after one year of trial period. The serialnumbers is GBW（E）10018.
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