青霉素类抗生素降解产物检测技术研究进展-食品安全质量检测学报-CSCIED科技核心评价数据库-手机版

青霉素类抗生素降解产物检测技术研究进展

Research progress on detection techniques for degradation products of penicillin antibiotics

ES评分 0 浏览量：261 下载量：0

DOI	10.19812/j.cnki.jfsq11-5956/ts.20250122002
刊名	食品安全质量检测学报 Journal of Food Safety and Quality
年，卷(期)	2025, 16(12)
作者	邱梓欣, 邱嘉艺, 卢宇帆, 刘凤银*,
作者单位	广东第二师范学院生物与食品工程学院
摘要	青霉素类抗生素被广泛应用于动植物疾病防控领域, 但由于使用不规范甚至违规使用, 导致食品中青霉素的残留。青霉素的分子结构不稳定, 不同条件下会产生不同程度的降解, 其降解产物如青霉噻唑酸等是其致敏性和细胞毒性的主要因素。且一旦发生降解, 原来针对青霉素原药的检测技术将无法准确反映实际情况。目前, 国内外对于青霉素类抗生素降解产物在食品安全方面的潜在风险尚未给予足够重视。本文总结了青霉素类抗生素在不同条件下的降解过程; 重点综述了高效液相色谱法、液相色谱-串联质谱法、免疫分析法以及表面增强拉曼光谱法在青霉素类抗生素降解产物检测中的具体应用; 同时分析了各类方法所具备的适用性特征以及存在的局限性, 以期提高对青霉素类抗生素降解产物残留所引发的食品安全问题的重视, 并为相关检测技术的进一步研究与发展提供参考。
Abstract	Penicillin antibiotics are widely used in the field of animal and plant disease prevention and control. However, due to improper or even illegal use, there are residues of penicillin antibiotics in food. The molecular structure of penicillin is unstable and undergoes varying degrees of degradation under different conditions. The degradation products, such as penicilloic acid, are the primary contributors to its allergenicity and cytotoxicity. And once penicillin degrades, conventional detection technologies for it will not accurately reflect the actual situation. At present, the potential risks of degradation products of penicillin antibiotics in food safety have not been given sufficient attention both domestically and internationally. This article summarized the degradation processes of penicillin antibiotics under different conditions, summarized the specific applications of high performance liquid chromatography, liquid chromatography-tandem mass spectrometry, immunoassay and surface-enhanced Raman spectroscopy in the detection of degradation products of penicillin antibiotics. Additionally, this paper analyzed the applicability characteristics and limitations of these methods to raise awareness of food safety issues caused by degradation products of penicillin antibiotics and provide references for further research and development of related detection technologies.
关键词	青霉素；降解产物；青霉噻唑酸
KeyWord	penicillin; degradation products; penicilloic acid
基金项目
页码	168-174

参考文献
相关文献

[1]耿响. 协同多黏菌素抗肺炎克雷伯菌化合物的筛选与评价
[D]. 北京: 中国农业科学院, 2024. GENG X. Screening and evaluation of synergistic compounds of colistin against Klebsiella pnenmoniae
[D]. Beijing: Chinese Academy of Agricultural Sciences, 2024.
[2]ZHANG QQ, YING GG, PAN CG, et al. Comprehensive evaluation of antibiotics emission and fate in the river basins of China: Source analysis, multimedia modeling, and linkage to bacterial resistance
[J]. Environment Science & Technology, 2015, 49(11): 6772–6782.
[3]胡瑞雪. 食品残留青霉素的热解产物青霉噻唑酸的毒性分析与评价
[D]. 长春: 吉林大学, 2024. HU RX. Toxicity analysis and evaluation of benzylpenicilloic acid, a pyrolytic product of penicillin residues in food
[D]. Changchun: Jilin University, 2024.
[4]周法庭, 朱晓丹, 波顺庆, 等. β-内酰胺环和侧链结构诱导青霉素类抗生素过敏的研究进展
[J]. 医学综述, 2018, 24(3): 444–448. ZHOU FT, ZHU XD, BO SQ, et al. Research progress on β-lactam ring and side chain structure inducing penicillin antibiotic allergy
[J]. Medical Review, 2018, 24(3) 444–448.
[5]KHANAA P, MOHD A, BANO S, et al. Spectrophotometric methods for the determination of ampicillin by potassium permanganate and 1-chloro-2,4-dinitrobenzen in pharmaceutical preparations
[J]. Arabian Journal of Chemistry, 2012, 53(2): 255–263．
[6]刘艳, 黄剑, 毛小凤, 等. 基于瑞利光散射技术检测肉食中残留氯唑西林
[J]. 分析科学学报, 2020, 36(2): 260–264. LIU Y, HUANG J, MAO XF, et al. Detection of chloracillin residues in meat based on rayleigh light scattering technology
[J]. Chinese Journal of Analytical Sciences, 2020, 36(2): 260–264.
[7]江月明. 致敏性青霉素降解物的酶联免疫检测方法研究
[D]. 天津: 天津科技大学, 2010. JIANG YM. Enzyme-linked immunassay for the determination of allergic degradation product of benzylpenicillin
[D]. Tianjin: Tianjin University of Science and Technology, 2010.
[8]CUI C, LU H J, HUI Q, et al. A preliminary investigation of the toxic effects of benzylpenicilloic acid
[J]. Food and Chemical Toxicology, 2018, 111: 567–577.
[9]周杰. 青霉素G在柑桔中降解代谢规律及其对品质的影响
[D]. 重庆: 西南大学, 2019. ZHOU J. Degradation behavior of penicillin G in citrus and its effect on fruit quality
[D]. Chongqing: Southwest University, 2019.
[10]高颀, 鲍晓瑾, 倪炜华. HPLC法定量测定原乳中青霉素钾酶解产物的研究
[J]. 中国测试, 2012, 38(2): 63–65. GAO Q, BAO XJ, NI WH. Study on determination of enzymatic hydrolysate from penicillin potassium in raw milk by HPLC
[J]. China Testing, 2012, 38(2): 63–65.
[11]农业农村部通告. 农业农村部关于印发《2019年动物及动物产品兽药残留监控计划》的通知
[EB/OL]. (2019-04-03)
[2024-04-21] http://www.xmsyj.moa.gov.cn/gzdt/201904/t20190410_6178507.htm Circular of the Ministry of Agriculture and Rural Affairs. Notice of the Ministry of Agriculture and Rural Affairs on printing and distributing the 2019 Veterinary drug residue monitoring plan for animals and animal products
[EB/OL]. (2019-04-03)
[2024-04-21] http://www.xmsyj.moa.gov.cn/ gzdt/201904/t20190410_6178507.htm
[12]肖惠贞, 刘红河, 尹江伟, 等. 高效液相色谱-串联质谱法测定乳制品中青霉素类药物及其主要代谢产物
[J]. 卫生研究, 2015, 44(4): 641–646. XIAO HZ, LIU HH, YIN JW, et al. Determination of penicilins and penicilloic acids in milk products by high performance liquid chromatography-tandem mass spectrometry
[J]. Health Research, 2015, 44(4): 641–646.
[13]SCHWARTZ MA. Mechanism of degradation of penicillin G in acidic solution
[J]. Journal of pharmaceutical sciences, 1965, 54(3): 472–480.
[14]SCHNEIDER C, DE WA. A new chemical aspect of penicillin allergy: The direct reaction of penicillin with ?-amino-groups
[J]. Nature, 1965, 208(5005): 57–59.
[15]HOU JP, POOLE JW. β-lactam antibiotics: Their physicochemical properties and biological activities in relation to structure
[J]. Journal of Pharmaceutical Sciences, 1971, 60(4): 503–532.
[16]BLAHA JM, KNEVEL AM, KESSLER DP, et al. Kinetic analysis of penicillin degradation in acidic media
[J]. Journal of Pharmaceutical Sciences, 1976, 65(8): 1165–1170.
[17]梁伟姿. 拉曼光谱技术在抗生素药物领域的应用
[D]. 天津: 天津大学, 2012. LIANG WZ. The application of Raman spectroscopy in antibiotic drugs
[D]. Tianjin: Tianjin University, 2012.
[18]DEGELAEN JP, LOUKAS SL, FEENEY J, et al. A nuclear magnetic resonance study of the degradation of penicillin G in acidic solution
[J]. Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry, 1979(1): 86–90.
[19]FADI A, DANIELE C, MATTHEW S, et al. Identification of penicillin G metabolites under various environmental conditions using UHPLC- MS/MS
[J]. Journal of Agricultural and Food Chemistry, 2016, 64(31): 6100–6107.
[20]LEVINE BB. Degradation of benzylpenicillin at pH 7.5 to D-benzylpenicilloic acid
[J]. Nature, 1960, 187(4741): 939–940.
[21]GRUNWALD L, PETZ M. Food processing effects on residues: Penicillins in milk and yoghurt
[J]. Analytica Chimica Acta, 2003, 483(1-2): 73–79.
[22]王冰. 青霉素菌渣肥的制备及其土壤施肥的环境安全性研究
[D]. 哈尔滨: 哈尔滨工业大学, 2018. WANG B. Prwparation of penicillin mycelium fertilizer and its environmental safety study following soil application
[D]. Harbin: Harbin Institute of Technology, 2018.
[23]崔成. 动物性食品中青霉素G钠残留的热加工风险评估
[D]. 长春: 吉林大学, 2018. CUI C. The risk assessment of benzylpenicillin G residue in heat-treated animal food products
[D]. Changchun: Jilin University, 2018.
[24]温玉麟. 青霉素的稳定性
[J]. 中国药学杂志, 1964(9): 388–397. WEN YL. Stability of penicillin
[J]. Chinese Journal of Pharmaceutical Sciences, 1964(9): 388–397.
[25]潘祖亭, 颜承农, 王润涛. 金属离子催化β-内酰胺类抗生素水解的荧光光谱研究
[J]. 分析试验室, 2001(4): 1–5. PAN ZT, YAN CN, WANG RT. Study on catalyzed hydrolysis of β-lactams antibiotics by metal ions with spectrofluorimetry
[J]. Analytical Laboratory, 2001(4): 1–5.
[26]CHEN JB, SUN PZ, ZHOU XF, et al. Cu(II)-catalyzed transformation of benzylpenicillin revisited: The overlooked oxidation
[J]. Environmental Science & Technology, 2015, 49(7): 4218–4225.
[27]MAI L N, KOO Y. Enzymatic hydrolysis of penicillin and in situ product separation in thermally induced reversible phase-separation of ionic liquids/water mixture
[J]. Enzyme and Microbial Technology, 2014, 63: 34–38.
[28]杜佳欣. 基于质量源于设计理念对青霉素杂质谱分析方法的优化
[D]. 北京: 中国食品药品检定研究院, 2021. DU JX. Optimization of the penicillin impurity spectrometry analysis method based on quality-by-design concept
[D]. Beijing: China Institute for Food and Drug Control, 2021.
[29]苏敏, 王利刚, 张磊, 等. 乳及乳制品中β-内酰胺酶抑制剂检测方法的研究进展
[J]. 食品安全质量检测学报, 2018, 9(4): 769–775. SU M, WANG LG, ZHANG L, et al. Research on the detection methods of β-lactamases inhibitors in milk and milk products
[J]. Journal of Food Safety & Quality, 2018, 9(4): 769–775.
[30]VASI K, PRIMOI M, KNEZ E, et al. Degradation pathway of penicillin by immobilized β-lactamase
[J]. Chemical Engineering Transactions, 2024, 1: 110.
[31]黄志宁, 郭新东, 寻知庆, 等. 食用植物油中安全风险物质的研究进展
[J/OL]. 现代食品科技, 1–12.
[2024-04-24]. https://doi.org/10.13982/ j.mfst.1673-9078.2025.1.1474 HUANG ZN, GUO XD, XUN ZQ, et al. Advances in research on safety risk substances in edible vegetable oils
[J/OL]. Modern Food Science and Technology, 1–12.
[2024-04-24]. https://doi.org/10.13982/j.mfst.1673- 9078.2025.1.1474
[32]冯桂蓉, 李红, 黄先亮, 等. 基于色谱技术的食品中多环芳烃检测方法研究进展
[J]. 分析测试学报, 2024, 43(12): 2031–2042. FENG GR, LI H, HUANG XL, et al. Advance in chromatographic techniques for polycyclic aromatic hydrocarbons detection in food
[J]. Journal of Analytical Testing, 2024, 43(12): 2031–2042.
[33]SHARKASY MEE, ABOSHABANA R, TOLBA MM, et al. A factorial-design/assisted HPLC method for simultaneous monitoring of phenytoin, trimethoprim, and sulphamethoxazole in plasma samples to optimize therapy and mitigate toxicity risks
[J]. Microchemical Journal: Devoted to the Application of Microtechniques in all Branches of Science, 2024, 206: 111462.
[34]李鹏娟, 许洪波, 杨远贵. 现代分析技术在天然产物立体异构体研究中的应用
[J]. 药物分析杂志, 2024, 44(10): 1647–1654. LI PJ, XU HB, YANG YG. Application of modern analytical techniques to the study of stereoisomers of natural products
[J]. Journal of Pharmaceutical Analysis, 2024, 44(10): 1647–1654.
[35]陈夏琴, 陈晓明, 刘颖, 等. 西罗莫司新类似物FIM-R140的分离和结构鉴定
[J]. 中国抗生素杂志, 2024, 49(9): 1013–1018. CHEN XQ, CHEN XM, LIU Y, et al. Isolation and structural identification of the sirolimusin analogue FIM-R140
[J]. Chinese Journal of Antibiotics, 2024, 49(9): 1013–1018.
[36]范筱京, 冯月超, 贾丽. HPLC法测定牛奶中青霉噻唑酸
[C]. 中国化学会, 中国化学会第28届学术年会第9分会场摘要集, 2012. FAN XJ, FENG YC, JIA L. Determination of penicilloic acid in milk by HPLC
[C]. Chinese Chemical Society, Abstract Collection of the 9th Session of the 28th Annual Conference of the Chinese Chemical Society, 2012.
[37]陈晨, 吴建欣, 王宗义, 等. 液相色谱-串联质谱法检测干熏鱼中的4种非挥发性亚硝胺
[J]. 食品安全质量检测学报, 2025, 16(7): 87–93. CHEN C, WU JX, WANG ZY, et al. Determination of 4 kinds of non-volatile nitrosamines in dried smoked fish by liquid chromatography-tandem mass spectrometry
[J]. Journal of Food Safety & Quality, 2025, 16(7): 87–93.
[38]吕锦绣, 颜楠, 徐文俊, 等. 7种抗肿瘤药物血药浓度测定方法建立及临床应用
[J]. 中国药房, 2025, 36(4): 475–481. LV JX, YAN N, XU WJ, et al. Determination method of plasma concentrations of 7 anti-tumor drugs and its application
[J]. China Pharmacy, 2025, 36(4): 475–481.
[39]GOESSENS T, HUYSMAN S, DE-TROYER N, et al. Multi-class analysis of 46 antimicrobial drug residues in pond water using UHPLC-Orbitrap-HRMS and application to freshwater ponds in Flanders, Belgium
[J]. Talanta, 2020, 220: 121326.
[40]LONG Z, ZHAO Z, FAN X, et al. Comparison of analytical-flow, micro-flow and nano-flow LC-MS/MS for sub-proteome analysis
[J]. Journal of Pharmaceutical and Biomedical Analysis, 2025, 252: 116484.
[41]SUHENDRA M, JULIANDI B, DARUSMAN HS, et al. Phytochemical analysis and antioxidant activity from Phanera semibifida stem and leaves extracts using LC-MS/MS
[J]. Biodiversitas: Journal of Biological Diversity, 2025, 26(1): 500–508.
[42]路杨, 王丽英, 秦振顺, 等. 超高效液相色谱-串联质谱法测定牛奶中4种β-内酰胺类抗生素及其主要代谢产物
[J]. 食品安全质量检测学报, 2021, 12(5): 1662–1668. LU Y, WANG LY, QIN ZS, et al. Determination of 4 kinds of β-lactam antibiotics and their main metabolites in milk by ultra performance liquid chromatography tandem mass spectrometry
[J]. Journal of Food Safety & Quality, 2021, 12(5): 1662–1668.
[43]LI J, SHIMKO K M, HE C, et al. Direct injection liquid chromatography-tandem mass spectrometry as a sensitive and high-throughput method for the quantitative surveillance of antimicrobials in wastewater
[J]. Science of the Total Environment, 2023, 900: 165825.
[44]刘红河, 廖仕成, 康莉, 等. 超高效液相色谱-四极杆串联线性离子阱质谱法测定乳制品中8种青霉素类药物及其主要代谢产物
[J]. 中国食品卫生杂志, 2016, 28(2): 192–199. LIU HH, LIAO SC, KANG L, et al. Determination of eight penicilins and its penicilloic acids in milk products by ultra performance liquid chromatography-hybrid triple quadrupole linear ion trap-mass spectrometry
[J]. Chinese Journal of Food Hygiene, 2016, 28(2): 192–199.
[45]苏敏, 李红丽, 白亚敏, 等. 基于液相色谱-串联高分辨质谱技术的食品中污染物检测技术研究进展
[J]. 食品安全质量检测学报, 2025, 16(4): 44–52. SU M, LI HL, BAI YM, et al. Research progress on contaminant detection technology in food based on liquid chromatography-tandem high resolution mass spectrometry
[J]. Journal of Food Safety & Quality, 2025, 16(4): 44–52.
[46]PRATYUSHA BB, SAMUVEL RMS, NIVETHA S, et al. LC-HRMS analysis of corn mint Mentha arvensis L. for anticancer activity against triple-negative breast cancer targeting inflammatory and apoptosis signaling pathways
[J]. New Journal of Chemistry, 2024, 48(2): 760–769.
[47]SOLORZANO E R, ROVERSO M, BOGIALLI S, et al. Antioxidant activity of Zuccagnia-type propolis: A combined approach based on LC-HRMS analysis of bioanalytical-guided fractions and computational investigation
[J]. Food Chemistry, 2024, 461: 140827.
[48]KIZILTAS H, ORTAAKARSU AB, BINGOL, et al. Sage (Salvia macrochlamys): LC-HRMS for phytochemical analysis, cytotoxicity, enzyme inhibition, antioxidant activity, molecular docking and molecular dynamics simulations
[J]. Plant Biosystems, 2024, 158(5): 1057–1075.
[49]赵凤娟, 岳振峰, 张毅, 等. 高效液相色谱-四级杆/静电场轨道阱高分辨质谱研究人工“无抗奶”中青霉素类药物的降解产物
[J]. 食品安全质量检测学报, 2014, 5(2): 339–351. ZHAO FJ, YUE ZF, ZHANG Y, et al. Degradation products study of penicillins in artificial “non-anti-milk” by high performance liquid chromatography-linear trap quadrupole-orbitrap mass spectrometry
[J]. Journal of Food Safety & Quality, 2014, 5(2): 339–351.
[50]CHIESA LM, CESARE FD, NOBILE M, et al. Antibiotics and non-targeted metabolite residues detection as a comprehensive approach toward food safety in raw milk
[J]. Foods, 2021, 10(3): 544.
[51]HORNBECK PV. Enzyme-linked immunosorbent assays
[J]. Current Protocols in Immunology, 2015(110): 211–213
[52]ZONG L, JIAO Y, GUO X, et al. Based fluorescent immunoassay for highly sensitive and selective detection of norfloxacin in milk at picogram level
[J]. Talanta, 2019, 195: 333–338.
[53]XIANG XR, YE QH, SHANG YT, et al. Quantitative detection of aflatoxin B1 using quantum dots-based immunoassay in a recyclable gravity-driven microfluidic chip
[J]. Biosensors and Bioelectronics, 2021, 190: 113394.
[54]ZHANG Y, JIANG YM, WANG S. Development of an enzyme-linked immunosorbent assay to detect benzylpenicilloic acid, a degradation product of penicillin G in adulterated milk
[J]. Journal of Agricultural and Food Chemistry, 2010, 58(14): 8171–8175.
[55]王莹. 致敏性青霉素降解物定性免疫分析方法的研究
[D]. 天津: 天津科技大学, 2014. WANG Y. Qualitative immunoassay for the determination of allergic degradation product of benzyl penicillin
[D]. Tianjin: Tianjin University of Science and Technology, 2014.
[56]ZHANG D, HUANG L, LIU B, et al. Quantitative detection of multiplex cardiac biomarkers with encoded SERS nanotags on a single T line in lateral flow assay
[J]. Sensors & Actuators: B. Chemical, 2018, 277: 502–509.
[57]WANG LY, WANG XK, CHENG L, et al. SERS-based test strips: Principles, designs and applications
[J]. Biosens Bioelectron, 2021, 189: 113360.
[58]郑园园, 王建萍, 郝培应, 等. SERS免疫层析技术在快速检测领域的研究进展
[J]. 分析试验室, 2023, 42(8): 1107–1115. ZHENG YY, WANG JP, HAO PY, et al. Research progress of surface-enhanced Raman scattering (SERS)-based immunochromatography in rapid detection
[J]. Analytical Laboratory, 2023, 42(8): 1107–1115.
[59]张丽颖. 结构选择性SERS衬底的构筑及其对青霉素药物中青霉噻唑酸的快速检测
[D]. 南京: 南京医科大学, 2015. ZHANG LY. The construction of structure-selective SERS substrates for the rapid detection of penicilloic acid in penicillin
[D]. Nanjing: Nanjing Medical University, 2015.
[60]El-ZAHRY MR, REFAAT IH, MOHAMED HA, et al. Utility of surface enhanced Raman spectroscopy (SERS) for elucidation and simultaneous determination of some penicillins and penicilloic acid using hydroxylamine silver nanoparticles
[J]. Talanta, 2015, 144: 710–716.
[61]MA Y, ZHANG M, LI L, et al. Study on the rapid limit test for six sulfonamide residues in food based on the TLC-SERS method
[J]. Molecules, 2024, 29(16): 3977.
[62]卢贝贝, 张晨杰, 徐敏敏, 等. 内置式薄层色谱-表面增强拉曼光谱联用基底的制备及在有机反应检测中的应用
[J]. 高等学校化学学报, 2025, 46(4): 16–22. LU BB, ZHANG CJ, XU MM, et al. Preparation of built-in thin layer chromatography-surface-enhanced Raman spectroscopy substrate and its application in organic reaction detection
[J]. Chemical Journal of Chinese Universities, 2025, 46(4): 16–22.

引用本文

邱梓欣, 邱嘉艺, 卢宇帆, 刘凤银*. 青霉素类抗生素降解产物检测技术研究进展 [J]. 食品安全质量检测学报. 2025; 16; (12). 168 - 174.

文献评论

相关学者

相关机构