張 毅，岳振峰，郭 文,2，吳紹精，沈金燦，肖陳貴，林 黎，華紅慧，侯樂錫，易冰清

動(dòng)物源性食品中藥物多殘留分析的研究進(jìn)展

張 毅1，岳振峰1，郭 文1,2，吳紹精1，沈金燦1，肖陳貴1，林 黎1，華紅慧1，侯樂錫1，易冰清1

（1.深圳出入境檢驗(yàn)檢疫局食品檢驗(yàn)檢疫技術(shù)中心，深圳市食品安全檢測技術(shù)研發(fā)重點(diǎn)實(shí)驗(yàn)室，深圳 518045；2.深圳大學(xué)化學(xué)與環(huán)境工程學(xué)院，深圳 518060）

近年來食品安全檢測領(lǐng)域的多殘留分析方法在分析通量、成本和適用性方面顯示了突出優(yōu)勢。動(dòng)物源性樣品基質(zhì)復(fù)雜、獸藥和遷移的農(nóng)藥殘留的濃度很低，以多殘留方式分析需要發(fā)展高效的樣品前處理方法和高選擇性的檢測技術(shù)。由于色譜-質(zhì)譜聯(lián)用技術(shù)在多殘留分析中有超過90%的應(yīng)用，本文綜述了近5 a來色譜-質(zhì)譜檢測的動(dòng)物源性食品的多殘留分析。

動(dòng)物源性食品；農(nóng)藥；獸藥；多殘留；色譜-質(zhì)譜聯(lián)用技術(shù)

隨著社會(huì)發(fā)展、人口增加和生活質(zhì)量的提高，人類對高質(zhì)量動(dòng)物蛋白的需求日益增長。動(dòng)物源食品在數(shù)量上滿足消費(fèi)者需求的同時(shí)其安全性卻面臨著諸多問題和挑戰(zhàn)，例如規(guī)模化養(yǎng)殖提高了非治療用藥的比例、工業(yè)化增加了來自環(huán)境污染的隱患、現(xiàn)有檢測技術(shù)無法應(yīng)對層出不窮的藥物和非法添加物等[1-2]。獸藥、農(nóng)藥多殘留分析（以下簡稱“多殘留分析”）的任務(wù)是以一次分析過程同時(shí)獲得多種（類）物質(zhì)的化學(xué)組成和含量信息。盡管多殘留分析在效率和成本方面十分具吸引力，但是需要解決不同理化性質(zhì)物質(zhì)的同時(shí)提取、凈化、富集，確保靈敏度與單一殘留分析沒有顯著降低，以及操作簡便易行等問題。本文對近年來動(dòng)物源性食品中藥物殘留樣品前處理技術(shù)和檢測手段方面開展的研究進(jìn)行綜述。

1 樣品前處理方法

1.1 固相萃?。╯olid phase extraction，SPE）

多殘留分析發(fā)展初期多以兩種不同萃取機(jī)理的SPE串聯(lián)以吸附多類目標(biāo)化合物。例如C18和NH2柱順序串聯(lián)用于22 種合成激素的凈化[3]，但該方法的線性不佳，難以準(zhǔn)確定量。Shimelis等[4]發(fā)現(xiàn)石墨化碳黑（graphite carbon black，GCB）/N-丙基乙二胺復(fù)合SPE柱比單用PSA柱去除基質(zhì)中脂肪酸類雜質(zhì)的效果更好。但由于兩種填料凈化機(jī)理不同卻要在同一條件下萃取目標(biāo)化合物，包括上樣液、洗脫溶劑等實(shí)驗(yàn)條件都受到限制。傳統(tǒng)的硅膠基反相C18柱適用于低極性和中等極性化合物的分離富集，如非甾體抗炎藥、激素、氯霉素和殺蟲劑[5-7]。近年發(fā)展起來的聚合物材料如聚苯二乙烯-N-吡咯烷酮（如親水親油平衡值（hydrophile-lipophile balance，HLB））、苯磺酸基鍵合陽離子交換樹脂、季銨基鍵合陰離子交換樹脂，兼有親水-親脂、反相萃取或離子交換作用，較C18柱有更寬的萃取化合物范圍。例如豬肉中的四環(huán)素和喹諾酮僅需沉淀蛋白即可過HLB柱凈化，比C18柱有更好的回收率和凈化效果[8]。由于肝臟樣品含有甘油三酯和脂肪酸，聚醚類和三嗪類結(jié)構(gòu)的抗球蟲類藥物多殘留檢測采用堿性氧化鋁除脂再用HLB萃取凈化的效果要優(yōu)于單用HLB[9]。禁用藥物如β-受體激動(dòng)劑、鎮(zhèn)靜劑最低執(zhí)法限量（minimum required performance limits，MRPLs）小于1.0 μg/kg，采用反相萃取則氯丙嗪、地西泮、噴布特羅等弱極性藥物在上樣液中溶解不佳而回收率差，改用乙腈提取NH2柱正相萃取，凈化效果和回收率得到改善[10]。然而為了使不同pKa的藥物在SPE柱上保留和洗脫，上樣液需要遷就最敏感的分析物，例如同時(shí)檢測蝦肉中土霉素、磺胺、喹諾酮、三苯甲烷類染料和妥曲珠利砜等18 種藥物，要將pH值調(diào)節(jié)至3.2才能使染料和土霉素藥物在SPE上同時(shí)保留，即使如此，孔雀石綠和妥曲珠利亞砜的回收率只有約10%[11]。盡管具有復(fù)合功能的SPE可用于近百種獸藥多殘留的樣品前處理[12]，但受到化合物理化性質(zhì)差異影響，回收率差異較大，且通過優(yōu)化條件提高回收率的空間有限。表1列出了SPE用于動(dòng)物源食品中有機(jī)化學(xué)危害物多殘留的樣品前處理的主要文獻(xiàn)。由于SPE的凈化機(jī)理較為單一，難以滿足理化性質(zhì)差異較大的藥物的同時(shí)凈化、富集的需求。

表1 SPE在動(dòng)物源食品藥物多殘留的樣品前處理中的應(yīng)用Table 1 Application of SPE as sample pretreatment procedure in multiresidue drug analysis of animal-derived foods

1.2 基質(zhì)分散固相萃取（matrix solid phase dispersion，MSPD）

MSPD是一種通過研磨使樣品在填料表面充分分散和固載，將混合物填裝成柱，再以溶劑洗脫目標(biāo)物的凈化技術(shù)。MSPD技術(shù)關(guān)鍵在于樣品經(jīng)過研磨分散在吸附劑表面形成新的“層析層”，再以適當(dāng)?shù)娜軇┫疵撃繕?biāo)化合物。對于多數(shù)弱極性化合物通常選擇C18、C8或GCB吸附劑。Shao Bing等[21]比較了GCB、C18用于蛋、牛奶中雙酚A（bisphenol A，BPA）、壬基酚（nonylphenol，NP）和辛基酚（octylphenol，OP）的萃取結(jié)果，發(fā)現(xiàn)GCB對于強(qiáng)極性的BPA吸附性強(qiáng)難以洗脫，導(dǎo)致GCB對于BPA的萃取效果比C18要差。對于弱 極性化合物如有機(jī)氯和多氯聯(lián)苯類化合物，可采用弗羅里硅土研磨吸附再以二氯甲烷-正己烷（1∶1，V/V）洗脫，但后續(xù)需以離心進(jìn)一步去除雜質(zhì)[22]。以熱水洗脫是MSPD的另一個(gè)發(fā)展趨勢。Bogialli等[23]分別以不同溫度熱水洗脫氨基糖苷類和四環(huán)素類藥物，發(fā)現(xiàn)水溫高有利于大部分藥物的洗脫回收，但是過高水溫也導(dǎo)致部分分析物水解，需要在溫度和回收率之間選擇適當(dāng)?shù)钠胶恻c(diǎn)。當(dāng)分析物可在100 ℃水環(huán)境下穩(wěn)定存在，MSPD的回收率和萃取效率常優(yōu)于C18和液-液萃取凈化法，且通過控制熱水溫度可減少內(nèi)源性干擾物的共萃取[24]。MSPD僅需研磨、裝柱和洗脫步驟即可同時(shí)分離多種分析物[25-28]，但是對于動(dòng)物源性樣品中痕量藥物多殘留分析而言主要是初級凈化作用，后續(xù)需增加凝膠滲透色譜（gel permeation chromatography，GPC）、體積排阻色譜（size exclusion chromat ography，SEC）等進(jìn)一步凈化。

1.3 分散固相萃?。╠ispersive solid phase extraction，d-SPE）與QuEChERS（Quick、Easy、Cheap、Effective、Rugged、Safe）

d-SPE與MSPD的區(qū)別是吸附劑分散于樣品提取液而不是樣品基質(zhì)中進(jìn)行凈化。QuEChERS是一種由d-SPE發(fā)展來的新型樣品前處理技術(shù)。QuECh ERS是以有機(jī)溶劑提取樣品，再在含有藥物的乙腈層中加入過量的鹽和緩沖液進(jìn)行液液萃取，有機(jī)相再以d-SPE方法凈化。Dagnac等[29]以d-SPE方法實(shí)現(xiàn)了生鮮奶中44 種農(nóng)藥殘留的提取凈化，加標(biāo)質(zhì)量濃度為4 μg/L時(shí)，回收率為60%～113%，相對標(biāo)準(zhǔn)偏差為1%～15%。在對含脂肪樣品（如蛋、奶等）的農(nóng)藥殘留分析中，QuEChERS法比d-SPE法更高效，結(jié)果可信度更高[30]。Guo Bin等[31]采用d-SPE法凈化農(nóng)產(chǎn)品中的苯并咪唑類殺菌劑及其代謝產(chǎn)物，9 種不同基質(zhì)中大部分目標(biāo)化合物的回收率較好，平均回收率在70%～110%。QuEChERS技術(shù)在藥物多殘留分析中體現(xiàn)越來越多優(yōu)勢[32-34]。分別以SPE、MSPD和QuEChERS法提取和凈化于花粉、蜂蜜中極性差異較大的多種藥物殘留，結(jié)果表明以SPE法的極性（如甲胺磷）和非極性（如六氯苯）化合物回收率較低，MSPD法的非極性化合物的回收率較差，而QuEChERS幾乎可實(shí)現(xiàn)所有化合物都有較好的回收率[35]。Aguilera-Luiz等[36]用QuEChERS技術(shù)處理了以肉食為主的嬰幼兒食品和嬰幼兒配方奶粉中獸藥多殘留的檢測。QuEChERS方法具有準(zhǔn)確度高、分析速度快、操作 簡便的優(yōu)點(diǎn)，但存在低濃度的化合物分析回收較差的問題。本課題組以QuEChERS方法提取凈化了包括硝基咪唑、β-受體激動(dòng)劑、合成激素、氯霉素等五類40 種禁用藥物，通過濃縮提取液提高方法靈敏度，與選擇性強(qiáng)的液相色譜-串聯(lián)質(zhì)譜（liquid chromatography-tandem mass spectrometry，LC-MS/MS）聯(lián)用，方法性能滿足歐盟殘留分析要求[37]。

1.4 加速溶劑萃?。╝ccelerated solvent extraction，ASE）

ASE是一種施加較高的溫度和（或）壓力來提高溶劑沸點(diǎn)、增加溶劑與樣品接觸面從而實(shí)現(xiàn)快速高效提取的技術(shù)。研究證明了ASE適用于提取動(dòng)物肌肉、內(nèi)臟中的β-內(nèi)酰胺、大環(huán)內(nèi)酯、喹諾酮、磺胺、四環(huán)素、硝基咪唑等31 種抗生素[38]。為使提取效率更高，通常需要借助干燥劑和分散劑來減少樣品中殘留的水分，促進(jìn)提取溶劑在樣品中的滲透和分散。中性（堿性）氧化鋁、硅膠、弗羅里硅土、海砂是常用的固定相，Na2EDTA也被用于減少雜質(zhì)金屬離子對化合物的絡(luò)合作用[39]。Herranz等[40]將勻漿的雞蛋與硅藻土混合，以pH值為3.0的磷酸鹽-乙腈（50∶50，V/V）作為提取溶劑，在1 500 psi和70 ℃條件下分別靜態(tài)提取3 個(gè)5 min（平行提取5 min），恩諾沙星及其代謝物的提取回收率介于67%～90%之間，且無需進(jìn)一步凈化。提取溶劑對ASE的影響較大，分別比較了乙腈、正己烷-丙酮（2∶1，V/V）、環(huán)己烷-乙酸乙酯（1∶1，V/V）中萃取牛、豬、雞和魚肌肉109 種農(nóng)藥殘留，結(jié)果表明3 種提取溶劑對目標(biāo)化合物提取率總體差別不大，但乙腈提取液中的脂肪含量更低，共萃取雜質(zhì)較少[41]。另一方面，以熱水作為提取溶劑的加壓萃取也引起人們的關(guān)注[38]。由于水的介電常數(shù)（極性）可以顯著隨溫度升高而降低，因此在一定壓力條件下熱水（100～2 00 ℃）可以像有機(jī)溶劑一樣對中等極性化合物的進(jìn)行選擇性提取。但該方法不適用于熱不穩(wěn)定型的化合物，如大環(huán)內(nèi)酯[42]。Gentili等[43]將均質(zhì)樣品與C18吸附劑充分混合，在160 ℃、1 400 psi條件下以10 mL水靜態(tài)提取5 min。將提取液在－18 ℃條件下冷卻1 h以沉淀除去脂類雜質(zhì)，無需進(jìn)一步凈化即可以LC-MS/MS檢測。該方法實(shí)現(xiàn)了生肉和嬰兒食品中14 種磺胺類藥物的同時(shí)測定。盡管ASE技術(shù)在提取效率和環(huán)境友好方面具有明顯的優(yōu)勢，但是其離線性、非批量處理和設(shè)備昂貴等因素也制約了它在多殘留分析中的應(yīng)用。

1.5 微波輔助萃?。╩icrowave assistance extraction，MAE）

MAE是以微波透過樣品內(nèi)部使細(xì)胞從內(nèi)部破裂，樣品與溶劑充分接觸，同時(shí)溶劑吸收微波能快速升溫使得分析物快速進(jìn)入到提取相的一種樣品提取技術(shù)。當(dāng)以極性較低的溶劑提取藥物殘留，如甲苯、醚類、乙酸乙酯、丙酮和乙腈等，進(jìn)行微波萃取時(shí)微波能穿透樣品基質(zhì)而不發(fā)生任何耗散（萃取體系不被加熱）。Akhtar[44]比較了乙醇-異丙醇（88∶12，V/V）的MAE和丙酮的常規(guī)提取對雞蛋、雞肉中的抗球蟲藥物的萃取效果。結(jié)果證明MAE提取效率更高、有機(jī)溶劑用量和耗時(shí)更少。Hermo等[15]以0.3%磷酸-乙腈（75∶25，V/V）為提取溶劑、施加4 min的微波，實(shí)現(xiàn)了豬肉中9 種喹諾酮的同時(shí)萃取，且與采用SPE提取凈化的回收率無明顯差距，但效率卻大大提高。盡管MAE可實(shí)現(xiàn)在分子層面對樣品基質(zhì)進(jìn)行高效萃取，但受到樣品細(xì)胞被微波能爆破從而導(dǎo)致基質(zhì)更復(fù)雜的影響和提取溶劑選擇的限制，MAE未能在動(dòng)物源性食品藥物多殘留分析方面有更多應(yīng)用。

1.6 超臨界流體萃?。╯upercritical fluid extraction，SFE）

SFE是一種以處于臨界狀態(tài)下的流體為提取溶劑，利用流體在臨界點(diǎn)附近體系溫度和壓力的微小變化，使物質(zhì)溶劑度發(fā)生幾個(gè)數(shù)量級的突變性來實(shí)現(xiàn)對某些物質(zhì)的 選擇性提取和分離的技術(shù)。Pensabene等[45]采用SFE技術(shù)對雞蛋中的氯霉素殘留進(jìn)行提取與凈化，回收率為77.4%～86.6%。Dost等[46]通過填充塔超臨界流體萃取-常壓化學(xué)電離質(zhì)譜法檢測了牛奶中磺胺類藥物殘留。SFE技術(shù)具有處理樣品速度快、效率高、無溶劑等優(yōu)點(diǎn)，其缺點(diǎn)是實(shí)驗(yàn)條件的選 擇和優(yōu)化比較困難，可選 擇的萃取體系較少。

樣品前處理是有效減少雜質(zhì)干擾，提高檢測靈敏度和選擇性，提高分析測定效率、改善和優(yōu)化分析的重要環(huán)節(jié)。迄今為止，SFE技術(shù)因其穩(wěn)定性、通用性和成本優(yōu)勢，占 據(jù)了同類藥物多殘留分析的主導(dǎo)地位；基質(zhì)分散固相萃取和QuEChERS技術(shù)在多類藥物多殘留分析方面的應(yīng)用逐漸擴(kuò)大。超濾膜分離、ASE、MAE、SFE、分子印跡聚合物、固相微萃取、液相微萃取等技術(shù)在提升樣品前處理效率、改善提取率和環(huán)境友好等方面均有各自優(yōu)勢，在多殘留分析領(lǐng)域也有一定應(yīng)用。研究者們需要根據(jù)關(guān)注的藥物殘留種類、樣品基質(zhì)復(fù)雜程度和檢測手段的選擇性來選擇適合的樣品前處理方法。

2 多殘留分析檢測方法研究進(jìn)展

20世紀(jì)90年代，大氣壓電離技術(shù)（atmosphere pressure ionization，API）的出現(xiàn)成功解決了液相色譜與質(zhì)譜間的接口問題，LC-MS在有機(jī)化合物定性定量分析方面一展 身手。迄今為止，運(yùn)用經(jīng)典的氣相色譜-質(zhì)譜（gas chromatography-mass spectrometry，GC-MS）和LC-MS技術(shù)能檢測包括藥物、毒素、添加劑、環(huán)境污染物等在內(nèi)的90%以上的有機(jī)化合物，已成為食品安全領(lǐng)域的主流檢測技術(shù)。

2.1 LC-MS/MS

LC-MS/MS技術(shù)已在動(dòng)物源性食品，如肌肉[3,19,40,47-51]、內(nèi)臟[8,10,18,25,35,39,52-53]、血液[5,54]、蛋[21,55]、奶[14,29,56-61]、海產(chǎn)品[62-64]、蜂蜜[65-66]等中多殘留分析中有了較好的應(yīng)用。已報(bào)道LC-MS/MS技術(shù)已在動(dòng)物源食品中磺胺類、喹諾酮類、大環(huán)內(nèi)酯類、β-內(nèi)酰胺類、四環(huán)素類[7,38,48-49,63-65]抗生素、激素（合成激素、糖皮質(zhì)激素、非甾體類激素等）[3,14,19,21,51,58-59]、農(nóng)藥類[7,29,61,66]、抗球蟲和驅(qū)蟲類藥物[18,35,53,55]、β-受體阻斷劑和鎮(zhèn)靜劑[62,65]、阿維菌素類[25,51]、硝基呋喃類[47]、非甾體類抗炎藥[5,56]等藥物多殘留分析中有較好的應(yīng)用。例如鄧龍等[67]采用LC-MS/MS正負(fù)電離模式切換測定了雞肉、牛肉和豬肉中的16 種氨基甲酸酯殺蟲劑及其代謝物。Zhang Jing等[10]利用LC-MS/MS測定動(dòng)物組織中β-受體阻斷劑和鎮(zhèn)靜劑的多殘留。該方法的優(yōu)勢在于能一次同時(shí)對豬肝、豬腎、豬肉和牛肉樣品中的19 種β-受體阻斷劑和11 種鎮(zhèn)靜劑進(jìn)行篩查和確證，回收率在76.4%～118.6%之間。黎文茵等[20]使用LC-MS法檢測雞肝中全氟烷基酸（perfluoroalkyl acids，PFAs）的殘留，定量極限（limit of quantification，LOQ）為0.014～0.213 μg/kg，該方法靈敏度高，且重現(xiàn)性好。Kaufmann等[68]使用LC-MS/MS檢測多種基質(zhì)（豬肉、魚肉和牛肝臟及腎臟）中氨基糖苷類抗生素的殘留。各個(gè)基質(zhì)中的大部分化合物具有良好的回收率和相關(guān)系數(shù)。Deceuninck等[69]利用LC-MS/MS 對牛奶中20 種糖皮質(zhì)激素進(jìn)行測定。Meng Zhe等[70]同樣也用LC-MS/MS法對牛奶中8 種氟喹諾酮、5 種磺胺類藥和4 種乙?；x產(chǎn)物進(jìn)行檢測。Hu Ting等[71]也采用LC-MS/MS正負(fù)電離模式同時(shí)檢測了豬肉中30 種非甾體抗炎藥的殘留。Kung等[72]用LC-MS/MS對水產(chǎn)品中磺酰胺類多殘留藥物進(jìn)行檢測，CCα為1.49～ 10.90 μg/kg，CCβ為1.71～11.40 μg/kg。

2.2 液相色譜-四極桿線性離子阱質(zhì)譜（liquid chromatography coupled to quadrupole linea r ion trap mass spectrometry，LC-Qtrap/MS）

Qtrap是一種選擇性蓄積一定質(zhì)量范圍內(nèi)的離子，再通過碰撞誘導(dǎo)裂解電壓獲得碎片的質(zhì)譜技術(shù)。采用Qtrap技術(shù)可獲得二級、三級甚至MSn的質(zhì)譜碎片，大大增強(qiáng)質(zhì)譜確證的準(zhǔn)確性和選擇性，且背景噪音很低，有利于提高多殘留篩查的靈敏度和準(zhǔn)確性。早期的半定量多殘留方法采用“目標(biāo)契合度（fit-to-purpose）”的理念，即比較未知樣品與最低濃度質(zhì)控樣的峰面積（峰高）以及二級質(zhì)譜匹配度。如Cepurnieks等[73]成功利用超高液相色譜法耦合的混合四極-高分辨率軌道阱質(zhì)譜分析（ultra performance liquid chromatography coupled to hybrid quadrupole-high resolution orbitrap mass spectrometry，UPLC-Qtrap/MS）技術(shù)檢測牛奶和肉類中26 種抗生素多殘留藥物，回收率為83%～112%。Li Hui等[11]采用LC-ACPI-Qtrap/MS技術(shù)同時(shí)半定量分析了蝦肉中土霉素、磺胺、喹諾酮、三苯甲烷類染料和妥曲珠利砜等18 種藥物。張鴻偉等[74]采用LC-Qtrap/MS測定了蜂蜜中7 種痕量硝基咪唑類藥物及其代謝物，在5 min色譜分離后能檢測痕量水平（0.1 μg/kg）的目標(biāo)化合物。張鴻偉等[75]采用LC-Qtrap/MS同樣方法測定了肌肉中16 種同化甾體激素的殘留，一次進(jìn)樣就完成確證分析，方法快速、高效。與MS3相比，從QTrap-MS獲得的離子更穩(wěn)定，定量分析的偏差更小。但是這種高通量的驗(yàn)證手段得出的數(shù)據(jù)量較大，后續(xù)數(shù)據(jù)分析工作量很大。但對于復(fù)雜基質(zhì)樣品，在特征離子選擇中，一方面需要排除基質(zhì)干擾大的離子，另一方面離子阱在一定分辨率需求下，其掃描速率較慢，因此在相同的時(shí)間和掃描質(zhì)量范圍內(nèi)，它的定量精度要比串聯(lián)四極桿差。

2.3 液相色譜-飛行時(shí)間質(zhì)譜（liquid chromatographytime-of- flight mass spectrometry，LC-TOF/MS）

TOF/MS的質(zhì)量分析器是一個(gè)離子漂移管，利用離子加速后質(zhì)量越大，到達(dá)接收 器所用時(shí)間越長，從而把不同質(zhì)量的離子按m/z值大小進(jìn)行分離[76]。早期的TOF因分辨率和 靈敏度低而較少應(yīng)用于食品中危害物的分析中，隨著LC-TOF/MS、液相色譜-四級桿/飛行時(shí)間質(zhì)譜（liquid chromatography-quadrupole-time-of-flight mass spectrometry，LC-Q-TOF/MS）、LC-IT-TOF/MS技術(shù)的不斷發(fā)展，在動(dòng)物源性食品中有機(jī)化學(xué)危害物多殘留的篩查分析中已有廣泛應(yīng)用[12-13,15,76-81]。例如Peters等[12]采用LC-TOF/MS檢測了蛋、魚和肉中的獸藥殘留。該方法的優(yōu)勢在于適用于多種復(fù)雜基質(zhì)樣品，能同時(shí)篩選12 類（苯并咪唑類、大環(huán)內(nèi)酯類、青霉素類、喹諾酮類、磺胺類、四環(huán)素類、硝基咪唑類、鎮(zhèn)靜劑類、非甾體抗炎藥、抗球蟲類、離子載體類和氯霉素類），共100多種獸藥殘留。張潔等[82]建立了超高效液相色譜/高分辨飛行時(shí)間質(zhì)譜法（ultra-performance liquid chromatography coupled with high resolution time-of-flight mass spectrometry，UPLC-HRTOF/MS）結(jié)合數(shù)據(jù)庫檢測乳制品中19 種抗生素的方法，該方法質(zhì)量偏差小于5 mD。通過較窄的提取離子窗口降低了基質(zhì)效應(yīng)，避免假陰性檢測結(jié)果，且同位素峰形匹配度高，使鑒定更準(zhǔn)確，能同時(shí)對4 類（磺胺類、青霉素類、四環(huán)素類和大環(huán)內(nèi)酯類）抗生素進(jìn)行高通量篩查。虞銳鵬等[83]采用UPLC-Q-TOF/MS檢測太湖水域鯉魚、鯽魚、河蚌、白蝦、螄螺等水產(chǎn)品中的微囊藻毒素和節(jié)球藻毒素，該方法分離時(shí)間短、相對標(biāo)準(zhǔn)偏差小，檢出限（limit of detection，LOD）為5.0～10.0 μg/kg。張東雷等[84]建立LC-IT-TOF/MS檢測肉制品中的10 種堿性染料。該方法通過離子阱飛行時(shí)間質(zhì)譜進(jìn)行多級質(zhì)譜圖分析，既可排除基質(zhì)干擾、提高靈敏度達(dá)到準(zhǔn)確定量，又可準(zhǔn)確判斷結(jié)果避免假陽性誤判情況。LC-TOF/MS技術(shù)通過高分辨來去除基質(zhì)干擾，能有效鑒別質(zhì)量數(shù)非常接近的化合物，可以快速、高通量篩查目標(biāo)或未知化合物超標(biāo)的樣品，但由于線性范圍的局限性，TOF/MS技術(shù)的定量效果不如串聯(lián)質(zhì)譜。

LC-MS體現(xiàn)了色譜和質(zhì)譜優(yōu)勢的互補(bǔ)，且由于大部分藥物都適合以液-質(zhì)聯(lián)用進(jìn)行分析具有選擇性強(qiáng)、效率高和檢測通量大等優(yōu)點(diǎn)，在多殘留分析的應(yīng)用最為廣泛。

2.4 氣相色譜-質(zhì)譜聯(lián)用（gas chromatography-mass spectrometer，GC-MS/MS）

氣相色譜-質(zhì)譜聯(lián)用儀是最早實(shí)現(xiàn)商品化的色譜聯(lián)用儀器。包括GC-MS、GC-MS/MS、氣相色譜-離子阱質(zhì)譜（gas chromatography-ion trap mass spectrometry，GC-ITMS）、GC-TOF/MS在動(dòng)物源性食品農(nóng)藥多殘留分析中有著重要應(yīng)用[32,42,85-86]。鄭鋒等[87]采用GC-MS法對河豚魚、鰻魚和蝦中的191 種農(nóng)藥多殘留進(jìn)行測定，回收率為50.2%～120%。該方法操作簡便，自動(dòng)化程度高，重復(fù)性好，適用于水產(chǎn)品中上百種農(nóng)藥多殘留的檢測。Azzouz等[88]以GC-MS檢測雞蛋和蜂蜜中22 種藥物。該方法可檢測到雞蛋和鵪鶉蛋中水平為0.095～2.7 μg/kg的氟苯尼考、乙嘧啶、雌激素酮和17β-雌二醇。Munaretto等[89]采用GC-MS/MS技術(shù)檢測魚肉樣品中的農(nóng)藥多殘留物質(zhì)。汪洋等[90]采用GC×GC-TOF-MS對魚肉中的含鹵有機(jī)污染物進(jìn)行定性和定量的篩查，該方法能定性分析到GC-MS法難以辨識的化合物，準(zhǔn)確性高，但該方法的前處理操作耗時(shí)。由于GC-MS 分析樣品時(shí)必須經(jīng)過氣化，對于熱不穩(wěn)定、極性和大分子化合物檢測受到限制。

3 結(jié) 語

目前，動(dòng) 物源性食品有機(jī)化學(xué)危害物多殘留分析方法仍不能完全同時(shí)兼顧化合物范圍大、靈敏度高和操作簡便。發(fā)展高效、通用型樣品前處理技術(shù)與高通量、高選擇檢測方法是這一領(lǐng)域的發(fā)展趨勢。在樣品前處理技術(shù)中發(fā)展以化合物的物理化學(xué)共性進(jìn)行“門檻式”的選擇，例如可選擇某個(gè)范圍分子質(zhì)量的超濾膜技術(shù)，可富集特定官能團(tuán)化合物的分散液-液微萃取技術(shù)以及基于新型吸附材料的QuChERS技術(shù)等。在擴(kuò)大檢測化合物范圍方面，色譜-質(zhì)譜聯(lián)用 技術(shù)、高分辨-串聯(lián)質(zhì)譜技術(shù)作為多殘留檢測的主流分析方法有以下發(fā)展趨勢：新型填料技術(shù)的色譜柱和分離方法的應(yīng)用使得檢測的目標(biāo)化合物范圍更寬，研發(fā)混合離子源以擴(kuò)大可離子化的化合物范圍，發(fā)展直接電離技術(shù)無需色譜分離而直接離子化后進(jìn)行質(zhì)譜分析。研發(fā)適用于高分辨質(zhì)譜篩查檢測技術(shù)高效的分析軟件，從海量的基礎(chǔ)數(shù)據(jù)中快速、準(zhǔn)確地得出檢測結(jié)果，將使得多殘留分析在質(zhì)量和效率上達(dá)到新的層次。動(dòng)物源性食品有機(jī)化學(xué)危害物多殘留檢測技術(shù)的發(fā)展很快，相關(guān)法規(guī)、標(biāo)準(zhǔn)也不斷完善，其應(yīng)用范圍和層次也不斷提升，對維護(hù)食品安全和人類健康有著重要的意義。

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Progress in Multiresidue Analysis of Veterinary Drugs in Foods of Animal Origin

ZHANG Yi1, YUE Zhenfeng1, GUO Wen1,2, WU Shaojing1, SHEN Jincan1, XIAO Chengui1, LIN Li1, HUA Honghui1, HOU Lexi1, YI Bingqing1
(1. Shenzhen Key Laboratory of Detection Technology R&D on Food Safety, Food Inspection Cente r of Shenzhen Enter-Exit Inspection and Quarantine Bureau, Shenzhen 518045, China; 2. College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen 518060, China)

In recent years, multiresidue drug analysis in the field of food safety shows outstanding advantages such as highthroughput detection, low cost and wide applicability. Animal-derived matrices are complicated, in which the concentration of residual veterinary drugs and migrating pesticides is very low. The development of efficient sample processing and high-sensitivity detection methods is highly necessary for the application of multiresidue drug analysis. Chromatography combined with mass spectrometry has been utilized for 90% of multiresidue drug analysis. In this article, we summarize the progress made in the development of sample pretreatment and analytical methods used for multi-residual drug analysis in foods of animal original by chromatography-mass spectrometry over the last five years.

animal-derived foods; pesticides; veterinary drug; multiresidues; chromatography-mass spectrometry

10.7506/spkx1002-6630-201601038

O656.22

A

1002-6630（2016）01-0213-09

張毅, 岳振峰, 郭文, 等. 動(dòng)物源性食品中藥物多殘留分析的研究進(jìn)展[J]. 食品科學(xué), 2016, 37(1): 213-221. DOI:10.7506/ spkx1002-6630-201601038. http://www.spkx.net.cn

ZHANG Yi, YUE Zhenfeng, GUO Wen, et al. Progress in multiresidue analysis of veterinary drugs in foods of animal origin[J]. Food Science, 2016, 37(1): 213-221. (in Chinese with English abstract) DOI:10.7506/spkx1002-6630-201601038. http://www.spkx.net.cn

2015-02-27

國家自然科學(xué)基金青年科學(xué)基金項(xiàng)目（21107074）；深圳市基礎(chǔ)研究項(xiàng)目（JCYJ2012061872144497）

張毅（1980—），女，高級工程師，博士，研究方向?yàn)樯V質(zhì)譜分析、樣品前處理和食品理化檢測。E-mail：sparkzy@163.com