Research Progress on Analysis and Detection Techniques of Veterinary Drug Residues in Animal Foods

Bing LI Xuzheng ZHOU Fusheng CHENG Xiaojuan WEI Weiwei Wang Jiyu ZHANG

Abstract As an important guarantee for the prevention and control of animal diseases, veterinary drugs have important functions in improving animal production performance and product quality and maintaining ecological balance. They are an important guarantee for the healthy development of animal husbandry, food safety and public health. However, the irrational use and abuse of veterinary drugs and feed pharmaceutical additives are widespread, causing harmful substances in animal foods and damage to human health, and threatening the sustainable development of the environment and animal husbandry as well. In order to ensure human health, it is urgent to develop a simple, rapid, high-sensitivity, high-throughput and low-cost veterinary drug residue detection technology. In this paper, the sample pretreatment methods and detection techniques for the analysis of veterinary drug residues in animal foods were reviewed.

Key words Animal food; Veterinary drug residue; Sample preparation; Detection techniques

As a large type of human foods, animal foods, including livestock and poultry meat, eggs, aquatic products, milk and their products, can provide proteins, fats, minerals and vitamins necessary for the human body. Veterinary drug residues in animal foods refer to the original form of veterinary drugs, their metabolites and related impurities accumulating or remaining in cells, tissues or organs of animals, or entering the milk of lactating animals or the eggs of laying eggs, or remaining in the ecological environment, after the use of veterinary drugs (including pharmaceutical additives). In recent years, there have been reports of veterinary drug residues causing food poisoning and affecting the export of livestock and poultry products, and it has gradually become a social hot issue that people are generally concerned about. Veterinary drug residues can not only directly cause acute and chronic toxic effects on human body and an increase in bacterial resistance, but also pose a serious threat to the environment and human health through the action of the environment and the food chain. The problems caused by veterinary drug residues have attracted wide attention from the international community and the attention of governments. China is a big country in the production, processing and consumption of livestock and poultry products. To ensure the quality and safety of animal products is related to the health of the people, the development of Chinas production and trade, and the sustained, healthy and rapid development of Chinas economy. Therefore, effective measures must be taken to reduce and control the occurrence of veterinary drug residues.

To ensure the quality and safety of animal foods and human health is inseparable from detection techniques. Animal food safety issues are becoming more and more prominent, and it is urgent to develop simple, rapid, high-sensitivity, high-throughput and low-cost veterinary drug residue detection techniques. Veterinary drug residue analysis and detection techniques have become a guarantee to promote the development of animal food standards in China, ensure the quality and safety of animal foods, and improve the international competitiveness of animal food in China. In this paper, the analysis and detection techniques of veterinary drug residues in animal foods were studied.

Pretreatment of Veterinary Drug Residues in Animal Foods

The residues of veterinary drugs are characterized by low levels of residues in the sample, and the sample matrixes are complex with many interfering substances, so it is difficult to separate and purify the residues. Sample preparation techniques are a key link in the analysis of veterinary drug residues, directly affecting the efficiency and accuracy of detection. Conventional sample preparation techniques have been replaced by some new isolation and purification methods such as solid phase extraction, solid phase microextraction, matrix solid-phase dispersion extraction, immunoaffinity chromatography, molecular imprinting technique and supercritical fluid extraction due to their cumbersome operation, poor stability and specificity. These new techniques have the characteristics of low sample size, good method specificity and selectivity, automated processing, reduced manual operation, environmental friendliness, and low use of organic reagents.

Solid phase extraction (SPE)

Solid phase extraction is the use of a solid adsorbent to adsorb a target compound in a liquid sample, separate it from the matrix of the sample and the interfering compound, and then elute with the eluent to separate and enrich the target compound. It is a combination of liquid-solid extraction and liquid chromatography, which is mainly used for the separation, purification and concentration of micro or trace target compounds in complex samples［1］. Yang et al.［2］used the HLB extraction column to determine 11 tetracyclines and quinolones in waste water. The minimum detection limit of the method was 0.03 to 0.07 μg/ml. Wang et al.［3］established a  liquid-liquid extraction-solid phase extraction-gas chromatography-flame photometric detector method for the determination of coumaphos residue in beef, and investigated the extraction effects of Florisil solid phase extraction cartridge and ODS solid phase extraction cartridge, in which rthyl acetate was chosen as the eluent. It was found that using Florisil solid phase extraction cartridge in the purification process effectively eliminated the matrix effect and obtained a satisfactory recovery rate.

Solid phase microextraction (SPME)

Solid phase microextraction is a simple, fast, solvent-free sample preparation and pretreatment technique proposed by Prof. Pawliszyn and Arhturhe of the University of Waterloo, Canada in the late 1980s. It allows the to-be-tested component to diffuse and be adsorbed to the stationary phase coating on the surface of the quartz fiber through the heterogeneous phase balance between the substrate and the extraction phase, and then to separate and determine the to-be-tested component combining with gas chromatography (GC) or high performance liquid chromatography (HPLC) after adsorption equilibrium. Zhang et al.［4］proposed polymermonolitu microextraction (PMME) based on In-tube SPME, which can be used in conjunction with HPLC. The future development trend of solid phase microextraction technology is using the combination of new stationary phase with head space sample introduction and GC to analyze volatile drugs, and expanding the application range of this technology［5］. SPME combined with GC is suitable for the analysis of volatile organic compounds, during which the components to be tested are separated from the extracted fibers by thermal release. For non-volatile organic compounds, SPME and HPLC can be used in combination to realize the detection, but adsorption and desorption are adopted to purify the sample, which results in poor quantitative accuracy.

Supercritical fluid extreaction (SFE)

Supercritical fluid extraction is a process in which a fluid in a supercritical state is used as an extraction solvent to separate a mixture by utilizing the high permeability of the fluid in this state. Supercritical fluids have high solubility and good flow, transfer and permeability properties, and can replace traditional toxic, flammable and volatile organic solvents. The biggest advantage of SFE is that it has high extraction efficiency, can continuously extract the target substance, and can reduce the environmental pollution caused by adjusting the temperature and pressure and adding an appropriate polar regulator to extract a certain target substance. Martin et al.［6］applied supercritical fluid CO2 extraction combined with SCX-SPE purification to study 10 benzimidazole veterinary drug residues in animal liver. The intra-group and inter-group relative standard deviations were less than 10% and 32%, respectively, and the detection limit was  0.05 mg/kg.  Danaher et al.［7］applied SFE to purify ivermectin, eprinomectin, avermectin and other drugs in animal liver. Shen et al.［8］established a supercritical fluid extraction (SFE)-high performance liquid chromatography (HPLC) method to simultaneously detect four fluoroquinolones (FQs) in chicken meat. The suitable conditions for SFE extraction are temperature 80 ℃, system pressure 300 kg/cm2, total flow rate 3 ml/min, extraction time 30 min, and entrainer (methanol) ratio 30%. The method is simple, economical and effective.

Ultrasonic-assisted extraction (SAE)

Ultrasonic-assisted extraction is a method which applies ultrasonic wave to accelerate the chemical reaction of substances, or to initiate new reaction pathways, or to improve physical and chemical properties such as dissolution and crystallization distribution, in order to increase the yield of chemical reactions to obtain new chemical reaction substances or to improve the separation and extraction efficiency of substances. In the detection of veterinary drugs, it can greatly promote solvent extraction of target components, thereby improving analysis efficiency［9］.   Kang et al.［10］established ultrasonic-microwave-assisted extraction-high performance liquid chromatography for simultaneous detection of four non-steroidal anti-inflammatory drug residues in mutton tissue, namely flunixin meglumine, meloxicam, diclofenac sodium and ketoprofen. The method is simple, rapid and sensitive, and meets the requirements of qualitative and quantitative analysis. Chen et al.［11］used ultrasonic assisted extraction technique to process milk  powder samples, and tested the experimental conditions of extraction time, amount of extracting solution and ultrasonic power. The optimal sample pretreatment conditions were: HNO3  5.00 ml, H2O2 4.00 ml, ultrasonic power 140 W and ultrasonic extraction time 30 min.

Microwave-assisted solvent extraction (MAE)

Microwave-assisted extraction applies microwave heating to accelerate the extraction of a target substance from a solid sample by a solvent. The outstanding advantage is that the solvent is used in a small amount and is fast, and it can simultaneously measure a plurality of samples with high extraction efficiency using the device which is simple and easy to operate［7］. Li et al.［12］applied microwave saponification extraction-gas chromatography to determine the PCBs in biological samples, and achieved a recovery rate of  84.1% with a relative standard deviation of 2.7%. The method is fast, efficient, and reduces the use of organic solvents. Huang  et al.［13］extracted polysaccharides from Smilax glabra L. under the assistance of microwave, with short extraction time and high extraction rate. Yu et al.［14］performed extraction by the microwave-assisted extraction technique and established a method for detecting chloramphenicol residue in animal foods combining with gas chromatography-mass spectrometry. The detection method showed a recovery rate of 76.2%-94.7%, a relative standard deviation of 6.1%-8.6%, and a minimum detection concentration of 0.1 μg/kg.

Matrix solid-phase dispersion (MSPD)

Matrix solid-phase dispersion is a sample preparation technique used in the analysis of trace compounds, which can be directly applied to extract target compounds from solid, semi-solid and viscous matrix samples. It has the advantages of less sample and solvent, short analysis time and one-step completion of extraction and purification process. Gentili et al.［15］used C18 as a dispersant to extract sulfonamides from meat and baby foods with hot water at 160 ℃ and 100 atmospheres.

Molecular imprinting (MI)

Molecular imprinting technique is to first bond the template molecule to the polymer monomer by the bonding methods including covalent bonding and non-covalent bonding, then cross-link polymer monomers, and finally remove the template molecule from the polymer, after which the imprint of the template molecule is left inside the polymer. MISPE is mainly applied in pre-treatment processes such as separation and enrichment of micro and trace contaminants and drugs in environmental samples such as water and soil. Especially for highly polar drugs, MISPE technique has a good effect of eliminating matrix interference［16］. At present, there have been reports about molecularly imprinted solid phase extraction of cholesterol［17］and cephalosporins［18］in biological samples. Wang et al.［19］prepared an enrofloxacin molecularly imprinted polymer with enrofloxacin as template molecule, α-methacrylic acid as functional monomer and ethylene glycol dimethacrylate as crosslinker. With the molecularly imprinted polymer as a solid phase extraction material, the method of high performance capillary electrophoresis was applied to establish a method for the detection of enrofloxacin in chicken by molecularly imprinted solid phase extraction-high performance capillary electrophoresis.

Agricultural Biotechnology2019

Method for Detecting Veterinary Drug Residues in Animal Foods

High performance liquid chromatography (HPLC)

HPLC is an analytical and detection technique widely used in medicine, chemical industry, environment and other fields, and is general for detection of veterinary drug residues. Hou et al.［20］applied rapid separation column-high performance liquid chromatography to determine the residues of seven fluoroquinolone veterinary drugs in pork. The results showed that the main fluoroquinolone veterinary drugs can reach baseline separation within 3.5 min, the components to be tested and the peak area showed good linear relations in the range of 0.2-50 μg/ml, and the detection limit of the method was 2.5-4.6 ng/ml. Chen et al.［21］established an HPLC for the simultaneous detection of multiple residues such as tetracyclines and fluoroquinolone veterinary drugs in aquatic products, and found that eight antibiotics (oxytetracycline, tetracycline, chlortetracycline, sarafloxacin, enrofloxacin, danofloxacin, ciprofloxacin and monoxafloxacin) had good linearity in the range of 0.11-10 mg/L. Marilyn et al.［22］simultaneously detected five FQNs (danofloxacin mesylate, ciprofloxacin, enrofloxacin, difloxacin and sarafloxacin) and three kinds of tetracyclines in chicken muscle tissue by high performance liquid chromatography-fluorescence (HPLC-FLD). The detected residual amounts reached  0.5-5.0 μg/kg, which can meet the residue limit standards of FQNs in various countries and organizations.

Capillary electrophoresis (CE)

High-performance capillary electrophoresis is a new technique developed in recent years. Compared with the commonly used HPLC method, it has the characteristics of no need for high-pressure pumps, not affected by acids, alkalis and surfactants in running buffers, less solvent and sample consumption, fast separation, high separation efficiency, wide application range, strong selectivity, low instrument cost and so on. Hernandez et al.［23］applied non-aqueous capillary electrophoresis (NACE) to analyze enrofloxacin, ciprofloxacin, danofloxacin, difloxacin, mabufloxacin, flumequine and oxolinic acid in pig kidney and achieved a good separation effect. Hernandez et al.［24］applied capillary isotachophoresis capillary zone electrophoresis (ITP-CZE), which is simple and sensitive, to detect ciprofloxacin, enrofloxacin and flumequine in pig serum.  Wang et al.［25］established a high performance capillary electrophoresis (HPCE) method for the determination of three quinolones and two sulfonamides in chicken liver, and found that three fluoroquinolones and two sulfonamides can be completely separated within 10 min.

High performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)

UPLC-MS/MS has become a more advanced and actively used detection method for veterinary drug residues［26-30］, which has the advantages of high sensitivity, low sample volume and small matrix interference. Xu et al.［31］applied HPLC-MS to simultaneously detect 15 important anabolic hormone residues in beef samples. Jiang et al.［32］applied UPLC-MS/MS to determine 13 sulfonamide and 6 quinolone veterinary drug residues in animal tissues. Liu et al.［33］established an UPLC-MS/MS method for simultaneous detection of two penicillins (amoxicillin and penicillin G) and five major metabolites in beef, which adopted a gradient elution procedure, and performed detection in the positive ion multiple reaction monitoring (MRM) mode. One injection and analysis took 8 min, and quantification adopted the matrix matching and standard internal standard method. The detection limit of samples was 0.05-3.0 μg/kg (S/N>3), and the limit of quantification was 25 μg/kg (S/N>10). The method had high sensitivity and good repeatability.

Gas chromatography-mass spectrometry (GC-MS)

GC-MS mainly applies electron bombardment source (EI) and negative ion chemical source (NCI), and has high sensitivity and a detection limit of 0.1 μg/kg. Because chloramphenicol, thiamphenicol and florfenicol all have several fragment ions with high abundance after silanization, it is easy to identify them qualitatively, and GC-MS is a sensitive method for detecting residues of fenicol antibiotics. Nagaka et al.［34］applied GC-MS to detect chloramphenicol and florfenicol in the muscles of yellowtail, which has high detection sensitivity, but the process of derivatization in sample treatment is more complicated.  He et al.［35］established a  GC-MS method for the determination of propiconazole residues in 18 food matrices. The determination was performed using GC-MS electron impact ionization source and selective ion monitoring mode. The peak area of the propiconazole standard solution was linear with the concentration in the range of 0.02-5.0 mg/L  (r=0.999 5). The recovery of propiconazole was between 70% and 115% at the three addition levels of 0.01, 0.02 and 0.05 mg/L. The relative standard deviation (n=6) was less than  10.2%, and the detection limit (3S/N) was 0.004 mg/L. The method is fast, sensitive, accurate and reliable.

Immnuoaffinity chromatography (IAC)

IAC as an immunologic purging method is a chromatographic technique based on the specific reversible immunological binding reaction of antigen-antibodies. IAC usually only requires the one-step chromatography including sample loading, washing and elution to highly purify and concentrate trace specific samples in complex samples. It has the characteristics of strong specificity, large binding capacity, mild elution conditions, and easy regeneration of chromatographic columns, so it is very suitable for the separation and analysis of trace veterinary drug residues in complex samples. Domestic and foreign immunoaffinity chromatography in the detection of veterinary drug residues is mostly based on low molecular weight targets, which is also the development trend of veterinary drug residue detection technology. IAC is currently the sample treatment technique with largest purification and enrichment capacity, but due to the complex antibody preparation technique, the application of IAC is limited［36］. Cooper et al.［37］applied ELISA to the detect residues of sedatives such as phenothiazine, acepromazine and chlorpromazine, and the detection limits in  rabbit kidney tissues were 5, 5 and 20 μg/kg, respectively, indicating that the method is still a fast and sensitive multi-residue detection method. Cooper et al.［38］used ELISA to determine furazolidone metabolites in shrimps, and obtained a detection limit of  0.1 μg/kg. The sensitivity was significantly improved compared with liquid chromatography and LC/MS. Nan et al.［39］introduced fluorescent microspheres in conventional ELISA method, and realized simultaneously detection of such three types of residual substances as chloramphenicol, clenbuterol and estradiol. This method is more sensitive, less cross-reactive and wider in detection range than conventional ELISA methods, and the LDL values of the three were 40, 50 and 1 000 ng/L, respectively.

Biosensor

A biosensor is a device that comprises a transducer and a bio-sensitive component that are closely coupled to selectively and reversibly respond to a specific chemical or biologically active substance. Biosensors includes enzyme sensors, tissue sensors, microbial sensors, etc. Compared with conventional detection methods, biosensor detection technology has the advantages of high sensitivity, fast response, easy operation, high throughput and being suitable for on-site detection［40］. Biosensors have been widely used in the field of domestic food analysis, such as glucose sensors, vitamin C sensors, and sensors for measuring the freshness of fish and shrimp. In recent years, automated biosensors have become a hot spot in residue analysis［41］. Gaudin et al.［42］combined biosensors with immunoassays for the detection of penicillin antibiotics in milk. This method selects an antibody against ampicillin sensitive to open-lactam rings as a conjugate based on surface plasma resonance. There are two methods for opening lactam rings in experiments, one of which is the use of penicillinase and the other is the chemical method. The detection limits of the two different ring-opening methods are 33 and 12.5 g/L, respectively. When the chemical method is applied, the sensor is more sensitive, but the penicillinase ring-opening method makes the operation process simpler and the result more stable.

Capillary electrophoresis- laser-induced fluorescence (CE-LIF)

Laser-induced fluorescence (LIF) detection is one of the most sensitive detection techniques for capillary electrophoresis［43］. Semiconductor pumped solid-state laser is an emerging laser source, which has the advantages of high output power stability, long service life, low price, small size, and convenient maintenance, compared with gas laser. Capillary electrophoresis-laser-induced fluorescence detectors are used extensively in capillary  electrophoresis immunoassays, during which after labeling the components to be tested with fluorescent substances, they can be analyzed under the LIF detector through competitive or non-competitive mode. Capillary electrophoresis immunoassay is has a broad prospect in veterinary drug testing［44-45］.

At present, the sample pretreatment techniques and determination methods of veterinary drug residue analysis are constantly updated and perfected, and are developing in a fast, sensitive, accurate and efficient direction. New techniques are constantly applied and optimized and penetrate mutually, and will play a more important role in the analysis of veterinary drug residues, which is beneficial to the promotion of the modernization of Chinas veterinary medicine industry and ensure the safety of animal foods.

References

［1］YU H, YE JQ, YAN YB, et al. Pretreatment technology of veterinary drug residue analysis［J］. Veterinary Orientation, 2010, 11: 54-55. (in Chinese)

［2］YANG S, CHA J, CARLSON K. Simultaneous ext raction and analysis of 11 tetracycline and sulfonamide antibiotics in influent and effluent domestic wastewater by solid phase extraction and liquid chromatography electrospray ionization tandemmass spectrometry［J］. J Chromatogr A, 2005, 1097: 40253.

［3］WANG PL, GAO S, FAN L, et al. Study on determination of coumaphos in beef by gas chromatography with liquid liquid extraction and solid phase extraction［J］. Chinese Journal of Analysis Laboratory, 2007, 26(10): 5-10. (in Chinese)

［4］ZHANG M, WEI F, ZHANG YF, et al. Novel polymer monolith microextraction using a poly (methacrylic acid-ethylene glycol dimethacrylate) monolith and its application to simultaneous analysis of several angiotensin II receptor antagonists in human urine by capillary zone electrophoresis［J］. J Chromatogr A, 2006, 1102: 294-231.

［5］YANG HF, GE ZX, YU SL, et al. Solid phase extraction and its application in veterinary drug residue analysis［J］. Chinese Journal of Veterinary Drug, 2007, 41 (4): 34-36. (in Chinese)

［6］MARTIN D, OKEEFFE M, JEREMY D. Development and optimization of a method for the extraction of benzimidazoles from animal liver using supercritical carbon dioxide ［J］. Anal Chim Acta, 2003, (483): 313-324.

［7］DANAHER M, OKEEFFE M, GLENNON JD. Extraction and isolation of avermectins and milbemycins from liver samples using unmodified supercritical CO2 with in-line trapping on basic alumina［J］. J Chromatogr B: Biomed Sci Appl, 2001, 761(1): 115-123.

［8］SHEN JY, YIN HX, SHEN ZH, et al. Simultaneous determination of four fluoroquinolone residues in chicken muscle by supercritical fluid extraction and high performance liquid chromatography［J］. Food Science and Technology, 2007, 15(10): 210-212. (in Chinese)

［9］DING N, HUANG YJ, JIA JP, et al. Research progress on veterinary drug residue analysis and detection technology［J］. Science and Technology Innovation Herald, 2010, 17(1): 5-6. (in Chinese)

［10］KANG YF, ZOU SW, DUAN WP, et al. Simultaneous analysis of 4 non-steroidal anti-inflammatory drug residues in mutton muscle using high performance liquid chromatography assisted by ultrasonic-microwave extraction［J］. Chinese Journal of Chromatography, 2010, 23(11): 1056-1060. (in Chinese)

［11］CHEN WT, WEN CZ. Determination of metal elements in milk powder by ultrasonic extraction［J］. Chemical Industry Times, 2007, 21(1): 48-51. (in Chinese)

［12］LI GK, HE XQ, YANG Y, et al. Elimination of interference of organochlorine pesticides in determination of polychlorinated biphenyls in soil samples by microwave alkaline hydrolysis［J］. Chinese Journal of Analytical Chemistry, 2000, 28(1): 26-30. (in Chinese)

［13］HUANG SW, CHI RA, ZHANG YF. Process of extracting polysaccharides from Smilax glabra Roxb. by microwave-assisted method［J］. Lishizhen Medicine and Materia Medica Research, 2007, 18(11):  2649-2652. (in Chinese)

［14］YU H. Determination of chloramphenicol residues in foodstuffs of animal origin by GC-MS using microwave-assisted extraction［J］. China Animal Health Inspection, 2009, 26(11): 44-46. (in Chinese)

［15］GENTILI A, PERRET D, MARCHESE S, et al. Accelerated solvent extraction and confirmatory analysis of sulfonamide residues in raw meat and infant foods by liquid chromatography electrospray tandem mass spectrometry［J］. J Agric Food Chem, 2004, 52 (15): 4614-46241.

［16］ZHU XL, SUN L, LIU Q, et al. Research progress of molecular imprinting technique in the determination of veterinary drug residue［J］. Chinese Journal of Veterinary Drug, 2007, 41(6): 34-37. (in Chinese)

［17］LYU B, SHI D, ZHANG JH. Selective solid-phase extraction of cholesterol from different biological samples using different molecular imprinted polymers［J］. Journal of Huazhong University of Science and Technology: Medical Sciences, 2005, 34 (5): 639-643. (in Chinese)

［18］HUANG ZF, TANG YW. An investigation on clean-up of cephalosporins in biomedical sample by molecular imprinting technique［J］. Analytical Chemistry, 2005, 33(10): 1424-1426. (in Chinese)

［19］WANG XY, TAN HR, QI KZ, et al. Determination of enrofloxacin residue in chicken muscle using molecular imprinted solid phase extraction-high performance capillary electrophoresis［J］. Chinese Journal of Chromatography, 2010, 10(7): 1107-1110. (in Chinese)

［20］HOU X, DONG XC, YANG GY. Study on determination of seven fluoroquinolones in pork sample by rapid high performance liquid chromatography［J］. Journal of Yunnan Nationalities University: Natural Sciences Edition, 2007, 16(3): 225-227. (in Chinese)

［21］CHEN HH, DAI J, WANG HX, et al. Simultaneous multiresidue determination of tetracyclines and fluoroquinolones in fish muscle using high performance liquid chromatography［J］. Journal of Instrumental Analysis, 2008, 27(9): 951-955. (in Chinese)

［22］MARILYN JS, SUSAN EB, IXCHEL RH, et al. Simultaneous determination of fluoroquinolones and tetracyclines in chicken muscle using HPLC with fluorescence detection ［J］. J Chromatogr B, 2007, 846(1): 8-13.

［23］HERNANDEZ M, BORRULL F, CALULL M. Using nonaqueous capillary electrophoresis to analyze several quinolones in pig kidney samples［J］. Electrophoresis, 2002, 23(3): 506-511.

［24］HERNANDEZ M, AGUILAR C, BORRULL F. Determination of ciprofloxacin, enrofloxacin and flu mequine in pig plas ma samples by capillary isotachophoresis-capillary zone electrophoresis ［J］. J chromatogr B Analyt Technol Biomed Life Sci, 2002, 772(1): 163-172.

［25］WANG XY, TAN HR, XUE XH, et al. Simultaneous determination of residual fluoroquinolones and sulfonamides in chicken liver by high performance capillary electrophoresis［J］. Heilongjiang Agricultural Sciences, 2011, (2): 107-110. (in Chinese)

［26］HERRANZ S, MORENO-BONDI MC, MARAZUELA MD. Development of a new sample pretreatment procedure based on pressurized liquid extraction for the determination of fluoroquino lone residues in table eggs［J］. J Chromatogr A, 2007, 1140: 63-67.

［27］ZHANG J, PENG XR, WANG XJ, et al. Determination of metabolites of nitrofuran in sausage by hyphenation of high performance liquid chromatography and mass spectrometry in tandem［J］. Physical Testing and Chemical Analysis Part B (Chemical Analysis), 2007, 43(10): 858-860. (in Chinese)

［28］YUE ZF, LIN XY, TANG SB. Determination of 16 quinolone residues in animal tissues using high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry［J］. Chinese Journal of Chromatography, 2007, 25(4): 491-495. (in Chinese)

［29］QU JW, WU JS, CAI QR, et al. HPLC-ESI-MS determination of chloramphenicol in fish［J］. Physical Testing and Chemical Analysis, 2005, 41 (11): 799-801. (in Chinese)

［30］LIU PY, JIANG N, WANG YF. Simultaneous determination of sulfonamides and fluoroquinolones residues in chicken by high performance liquid chromatography-electrospray tandem mass spectrometry［J］. Chinese Journal of Chromatography, 2008, 26(3): 348-352. (in Chinese)

［31］XU TT, DAI J, CHEN SW, et al. Simultaneous determination of 15 anabolic hormone veterinary drug residues in beef by LC-MS/MS［J］. Food and Fermentation Industries, 2009, 35(8): 110-115. (in Chinese)

［32］JIANG S, ZHAO Y, JIN Y, et al. UHPLC-MS/MS determination of residual amounts of 19 veterinary drugs in animal tissues［J］. Physical Testing and Chemical Analysis Part B (Chemical Analysis), 2010, 46(1): 1319-1322. (in Chinese)

［33］LIU CJ, WANG H, DU ZX, et al. Simultaneous determination of 2 penicillins and their 5 major metabolites in bovine muscle by ultra performance liquid chromatography tandem mass spectrometry［J］. Chinese Journal of Analytical Chemistry, 2011, 39(5): 617-622. (in Chinese)

［34］NAGAKA T, OKA H. Detection of residual chloramphenicol, flofenicol, and thiamphenicol in yellow tail fish muscles by capillary gas chromatography-mass spectrometry［J］. J Agric Food Chem, 1996(44): 1280-1284.

［35］HE Q, LI JH, KONG XH, et al. GC2MS determination of residual amount of propiconazole in food stuffs with separation by solid phase extraction［J］. Physical Testing and Chemical Analysis, 2010, 46(2): 178-183. (in Chinese)

［36］YANG F, LI YP, LI XJ, et al. Determination of mabendazole residue in eel muscles by HPLC［J］. Chinese Journal of Health Laboratory Technology, 2004, 14(5): 545-546. (in Chinese)

［37］COOPER J, DEL AH AUT P, FODEY TL, et al. Development of a rapid screening test for veterinary sedatives and the beta-blocker carazolol in porcine kidney by ELISA［J］. Analyst, 2004, 129 (2): 169-174.

［38］COOPER KM, ELLIOTT CT, KENNEDY DG. Detection of 3-amino-2-oxazolidinone (AOZ), a tissue bound metabolite of the nitrofuran furazolidone, in prawn tissue by enzyme immunoassay［J］. Food Addit Contam, 2004, 21(9): 841-848.

［39］LIU N, SU P, GAO Z, et al. Simultaneous detection for three kinds of veterinary drug. Chloram phenicol clenbuterol and 17-beta-estradiol by high-throughput suspension array technology［J］. Analytica Chimica Acta, 2009, 632(1): 128-134.

［40］TOLDRA F, REIG M. Methods for rapid detection of chemical and veterinary drug residues in animal foods ［J］. Trends in Food Science＆Technology, 2006, 17: 482-489.

［41］GUSTAVSSON E, PETER B, STERNESJO A. Biosensor analysis of penicillin Ginmilk based on the inhibition of carboxy peptidase activity ［J］. Analytica Chimica Acta, 2002, 468(1): 153-159.

［42］GAUDIN V, FONTAINE J, MARIS P. Screening of penicillin residues in milk by a surface plasmon resonance-based biosensor assay comparison of chemical and enzymatic sample pretreatment ［J］. Analytica Chimica Acta, 2007, 436(2): 191-198.

［43］GUZMAN NA. Capillary electrophoresis teehnology［M］. NewYork: Mareel Dekker, 1993: 605-614.

［44］RAO QX, ZHAO ZH. Application of capillary electrophoresis in determination of multi-residues of veterinary drugs and pesticides［J］. Progress In Veterinary Medicine, 2008, 29(181): 24-27. (in Chinese)

［45］CAI YL, YANG JJ, WANG YF, et al. Determination of gabapentin  using capillary electrophoresis with laser-induced fluorescence detection［J］. Chinese Journal of Chromatography, 2010, 28 (12): 1179-1184. (in Chinese)