Article(id=1193259087325524515, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1193259081696772901, articleNumber=null, orderNo=null, doi=10.16438/j.0513-4870.2024-0995, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1728921600000, receivedDateStr=2024-10-15, revisedDate=1734192000000, revisedDateStr=2024-12-15, acceptedDate=null, acceptedDateStr=null, onlineDate=1762424736100, onlineDateStr=2025-11-06, pubDate=1741708800000, pubDateStr=2025-03-12, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1762424736100, onlineIssueDateStr=2025-11-06, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1762424736100, creator=13701087609, updateTime=1762424736100, updator=13701087609, issue=Issue{id=1193259081696772901, tenantId=1146029695717560320, journalId=1189982191388893191, year='2025', volume='60', issue='3', pageStart='533', pageEnd='842', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1762424734756, creator=13701087609, updateTime=1764224876724, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1200809424412602670, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1193259081696772901, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1200809424412602671, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1193259081696772901, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=791, endPage=800, ext={EN=ArticleExt(id=1193259087728177704, articleId=1193259087325524515, tenantId=1146029695717560320, journalId=1189982191388893191, language=EN, title=Determination of 53 prohibited veterinary drug residues in goat horn by salting-out assisted liquid-liquid extraction combined with UHPLC-MS/MS, columnId=1190335348761793317, journalTitle=Acta Pharmaceutica Sinica, columnName=Original Articles, runingTitle=null, highlight=null, articleAbstract=

A detection method using UHPLC-MS/MS was established for the determination of 53 prohibited veterinary drug residues in goat horns, including 16 tranquilizers, 14 β-agonists, chloramphenicol, 4 fluoroquinolones, 7 nitroimidazoles, 3 quinoxalines, and 8 other compounds. Samples were extracted using salting-out assisted liquid-liquid extraction (SALLE). A Zorbax Eclipse Plus C18 column (1.8 μm, 3.0 mm × 150 mm, Agilent) was used with 0.1% formic acid solution-acetonitrile as the mobile phase for gradient elution. Detection was performed in positive and negative electrospray ionization modes using multiple reaction monitoring (MRM). All 53 analytes showed good linearity within their respective concentration ranges, with correlation coefficients above 0.99. The average recoveries at three spiked levels ranged from 70.4% to 118.7%, with relative standard deviations (RSDs) ranging from 0.69% to 12.07%. The limits of detection (LODs) ranged from 0.1 to 50 μg·kg-1, and the limits of quantitation (LOQs) ranged from 0.2 to 100 μg·kg-1. This method has been applied to the determination of real samples.

, correspAuthors=Jian SUN, Qing HU, authorNote=null, correspAuthorsNote=null, copyrightStatement=Copyright ©2025 Acta Pharmaceutica Sinica. All rights reserved., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=Bai-hao LAO, Jian SUN, Jing-xian ZHANG, Hong YU, Ying-ying RAN, Fan HUANG, Shen JI, Qing HU), CN=ArticleExt(id=1193259246155428744, articleId=1193259087325524515, tenantId=1146029695717560320, journalId=1189982191388893191, language=CN, title=盐析辅助液液萃取-超高效液相色谱串联质谱法测定山羊角中53种禁用兽药残留, columnId=1190335348896011050, journalTitle=药学学报, columnName=研究论文, runingTitle=null, highlight=null, articleAbstract=

建立了UHPLC-MS/MS测定山羊角中53种禁用兽药残留的检测方法, 包括16种镇静剂类、14种β-受体激动剂类、氯霉素、4种氟喹诺酮类、7种硝基咪唑类、3种喹噁啉类化合物、8种其他类化合物。采用盐析辅助液液萃取样品, Zorbax Eclipse Plus C18色谱柱(1.8 μm, 3.0 mm × 150 mm, Agilent), 以0.1%甲酸溶液-乙腈为流动相, 梯度洗脱, 在电喷雾离子化正负离子模式下, 以多反应监测方式(MRM) 检测。53种待测物在各自浓度范围内均成良好线性关系, 相关系数均在0.99以上; 三水平平均加样回收率为70.4%~118.7%, 相对标准偏差(RSD) 为0.69%~12.07%, 检出限为0.1~50 μg·kg-1, 定量限为0.2~100 μg·kg-1。本方法已应用于实际样品的测定。

, correspAuthors=孙健, 胡青, authorNote=null, correspAuthorsNote=
*孙健, Tel: 18001678040, E-mail:
胡青, Tel: 18001677896, E-mail:
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School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
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Veterinary drug residues in animal-derived foods: sample preparation and analytical methods [J]. Foods, 2021, 10: 555., articleTitle=null, refAbstract=null), Reference(id=1194703709562184335, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1193259087325524515, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[2], rfOrder=1, authorNames=null, journalName=null, refType=null, unstructuredReference=Pratiwi R, Ramadhanti SP, Amatulloh A, et al. Recent advances in the determination of veterinary drug residues in food [J]. 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J Liq Chromatogr Relat Technol, 2015, 38: 1185-1193., articleTitle=null, refAbstract=null), Reference(id=1194703712703718069, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1193259087325524515, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[30], rfOrder=29, authorNames=null, journalName=null, refType=null, unstructuredReference=Liu R, Wang F, Huang Q, et al. Available sustainable alternatives replace endangered animal horn based on their proteomic analysis and bio-effect evaluation [J]. 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Rome: Codex Alimentarius Commission, 2014 [2024-09-30]. https://www.fao.org/fao-who-codexalimentarius/sh-proxy/en/?lnk=1&url=https%253A%252F%252Fworkspace.fao.org%252Fsites%252Fcodex%252FStandards%252FCXG%2B71-2009%252FCXG_071e_2014.pdf., articleTitle=null, refAbstract=null), Reference(id=1194703712900850360, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1193259087325524515, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[33], rfOrder=32, authorNames=null, journalName=null, refType=null, unstructuredReference=Sun QF, Zhang SE, Chen QZ, et al. Salting-out assisted liquid-liquid extraction for the simple and rapid determination of veterinary antibiotic residues in aquatic products by HPLC-MS/MS [J]. Food Chem, 2024, 460: 140775., articleTitle=null, refAbstract=null), Reference(id=1194703712972153529, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1193259087325524515, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[34], rfOrder=33, authorNames=null, journalName=null, refType=null, unstructuredReference=Tian T. Study on High Accuracy Measurement Method of β2-Agonist Residues in Animal Derived Food (动物源食品中β2-受体激动剂残留高准确度测量方法研究) [D]. Shanghai: Shanghai University of Engineering Science, 2021., articleTitle=null, refAbstract=null), Reference(id=1194703713077011130, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1193259087325524515, doi=null, pmid=null, pmcid=null, year=null, volume=null, issue=null, pageStart=null, pageEnd=null, url=null, language=null, rfNumber=[35], rfOrder=34, authorNames=null, journalName=null, refType=null, unstructuredReference=Zhang KM, Liang FY, Deng M, et al. Multi-residue determination of veterinary drugs in porcine muscle by QuEChERS and liquid chromatography-tandem mass spectrometry [J]. Chin J Chromatogr (色谱), 2016, 34: 860-867., articleTitle=null, refAbstract=null)], funds=[Fund(id=1194703709335691914, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1193259087325524515, awardId=21DZ2290200, language=CN, fundingSource=上海市科委研发平台专项(21DZ2290200), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1194703703954399774, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1193259087325524515, xref=null, ext=[AuthorCompanyExt(id=1194703703962788383, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1193259087325524515, companyId=1194703703954399774, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1. School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China), AuthorCompanyExt(id=1194703703966982688, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1193259087325524515, companyId=1194703703954399774, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.上海中医药大学中药学院, 上海 201203)]), AuthorCompany(id=1194703704050868770, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1193259087325524515, xref=null, ext=[AuthorCompanyExt(id=1194703704059257379, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1193259087325524515, companyId=1194703704050868770, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2. National Medical Products Administration Key Laboratory for Quality Control of Traditional Chinese Medicine, Shanghai Institute for Food and Drug Control, Shanghai 201203, China), AuthorCompanyExt(id=1194703704063451684, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1193259087325524515, companyId=1194703704050868770, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.上海市食品药品检验研究院, 国家药品监督管理局中药质量控制重点实验室, 上海 201203)])], figs=[ArticleFig(id=1194703708450693751, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1193259087325524515, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
CompoundCAS numberChemical formulaDissolved solventLot. numberPurityM.W.
β-Agonist
  Clorprenaline 3811-25-4 C11H16ClNO Methanol S177845 0.828 213.1
  Tulobuterol 41570-61-0 C12H18ClNO Methanol S139505 0.999 227.1
  Ractopamine 97825-25-7 C18H23NO3 Methanol S177845 0.989 301.2
  Bambuterol 81732-65-2 C18H29N3O5 Methanol S177845 0.993 367.2
  Phenylethanolamine A 1346746-81-3 C19H24N2O4 Methanol S148439 0.998 344.2
  Mabuterol 56341-08-3 C13H18ClF3N2O Methanol S177845 0.999 310.1
  Salbutamol 18559-94-9 C13H21NO3 Methanol S177845 0.994 239.2
  Zilpaterol 117827-79-9 C14H19N3O2 Methanol S177845 0.961 261.2
  Cimaterol 54239-37-1 C12H17N3O Methanol S172505 0.980 219.1
  Terbutaline 23031-25-6 C12H19NO3 Methanol S177845 0.999 225.1
  Clenbuterol 37148-27-9 C12H18Cl2N2O Methanol S177845 0.988 276.1
  Cimbuterol 54239-39-3 C13H19N3O Methanol S096141 0.999 233.2
  Brombuterol 41937-02-4 C12H18Br2N2O Methanol S134561 0.994 364.0
  Formoterol 73573-87-2 C19H24N2O4 Methanol S146953 0.999 344.2
Amphenicol
  Chloramphenicol 56-75-7 C11H12Cl2N2O5 Methanol S145561 0.998 322.0
Tranquilizer
  Chlorpromazine 50-53-3 C17H19ClN2S Methanol S167751 0.980 318.1
  Methaqualone 72-44-6 C16H14N2O Methanol ALT028069 0.999 250.1
  Xylazine 7361-61-7 C12H16N2S Methanol S159793 0.990 220.1
  Estazolam 29975-16-4 C16H11ClN4 Methanol S119943 0.999 294.1
  Midazolam 59467-70-8 C18H13ClFN3 Methanol S119943 0.994 325.8
  Triazolam 28911-01-5 C17H12Cl2N4 Methanol S119943 0.992 342.0
  Alprazolam 28981-97-7 C17H13ClN4 Methanol S119943 0.999 308.1
  Diazepam 439-14-5 C16H13ClN2O Methanol S119943 0.999 284.1
  Nitrazepam 146-22-5 C15H11N3O3 Methanol S119943 0.999 281.1
  Oxazepam 604-75-1 C15H11ClN2O2 Methanol S119943 0.996 286.1
  Clonazepam 1622-61-3 C15H10ClN3O3 Methanol S119943 0.999 315.0
  Lorazepam 846-49-1 C15H10Cl2N2O2 Methanol S119943 0.999 320.0
  Phenobarbital 50-06-6 C12H12N2O3 Methanol S142179 0.999 232.1
  Barbital 57-44-3 C8H12N2O3 Methanol S142179 0.999 184.1
  Amobarbital 57-43-2 C11H18N2O3 Methanol S142179 0.999 226.1
  Secobarbital 76-73-3 C12H18N2O3 Methanol S142179 0.999 238.1
Fluoroquinolone
  Norfloxacin 70458-96-7 C16H18FN3O3 Methanol S117199 0.999 319.1
  Pefloxacin 70458-92-3 C17H20FN3O3 Methanol S117199 0.987 333.2
  Lomefloxacin 98079-51-7 C17H19F2N3O3 Methanol S117199 0.904 351.1
  Ofloxacin 82419-36-1 C18H20FN3O4 Methanol S117199 0.995 361.1
Nitroimidazole
  Dimetridazole 551-92-8 C5H7N3O2 Methanol S169555 0.999 141.1
  Dimetridazole-2-hydroxy 936-05-0 C5H7N3O3 Methanol S169555 0.980 157.1
  Metronidazole-hydroxy 4812-40-2 C6H9N3O4 Methanol S169555 0.996 187.1
  Metronidazole 443-48-1 C6H9N3O3 Methanol S169555 0.999 171.1
  Ronidazole 7681-76-7 C6H8N4O4 Methanol S169555 0.990 200.1
  Ipronidazole 14885-29-1 C7H11N3O2 Methanol S094613 0.999 169.1
  Tinidazole 19387-91-8 C8H13N3O4S Methanol S143801 0.999 247.1
Quinoxaline
  2-Quinoxaline-carboxylic acid (2-QCA) 879-65-2 C9H6N2O2 Methanol S153963 0.950 174.0
  3-Methyl-2-quinoxaline-carboxylic acid (MQCA) 74003-63-7 C10H8N2O2 Methanol S160521 0.999 188.1
  Carbadox 6804-07-5 C11H10N4O4 Methanol/DMSO (3∶1) S095207 0.972 262.1
Others
  Dapsone 80-08-0 C12H12N2O2S Acetonitrile S125593 0.994 248.1
  Leucomalachite green 129-73-7 C23H26N2 Methanol S167117 0.994 330.2
  Malachite green 569-64-2 C23H25ClN2 Methanol S167117 0.981 364.9
  Clonidine 4205-90-7 C9H9Cl2N3 Methanol S146723 0.998 229.0
  Cyproheptadine 129-03-3 C21H21N Methanol S149739 0.998 287.4
  Carbofuran 1563-66-2 C12H15NO3 Acetonitrile 2250832 0.999 221.1
  Chlordimeform 6164-98-3 C10H13ClN2 Methanol S168431 0.989 196.1
  Fipronil 120068-37-3 C12H4Cl2F6N4OS Acetonitrile S163547 0.995 435.9
Internal standard (IS)
  Cimbuterol-d9 1246819-04-4 C13H10D9N3O Methanol G0065083 0.977 242.2
  Zilpaterol-d7 1217818-36-4 C14H12D7N3O2 Methanol G0088143 > 0.98 268.2
  2-QCA-d4 2244217-89-6 C9H2D4N2O2 Methanol H0095896 0.980 178.1
  Metronidazole-hydroxy-d2 2196180-19-3 C6H7D2N3O4 Methanol H3000662 0.980 189.1
  Pefloxacin-d5 1228182-51-1 C17H15D5FN3O3 Methanol F0058438 0.996 338.2
  Dapsone-d8 557794-38-4 C12H4D8N2O2S Methanol D0054643 1.000 256.1
  Carbofuran-d3 1007459-98-4 C12H12D3NO3 Methanol E0066530 0.998 224.1
  Fipronil-13C415N2 - C813C4H4Cl2F6N215N2OS Methanol A0069672 1.000 443.1
  Leucomalachite green-d6 1173021-13-0 C23H20D6N2 Acetonitrile G0093712 0.998 336.3
  Malachite green-d5 - C23H20D5ClN2 Acetonitrile G0093712 0.596 369.9
), ArticleFig(id=1194703708547162745, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1193259087325524515, language=CN, label=Table 1, caption=

The information of 53 analysts and internal standards

, figureFileSmall=null, figureFileBig=null, tableContent=
CompoundCAS numberChemical formulaDissolved solventLot. numberPurityM.W.
β-Agonist
  Clorprenaline 3811-25-4 C11H16ClNO Methanol S177845 0.828 213.1
  Tulobuterol 41570-61-0 C12H18ClNO Methanol S139505 0.999 227.1
  Ractopamine 97825-25-7 C18H23NO3 Methanol S177845 0.989 301.2
  Bambuterol 81732-65-2 C18H29N3O5 Methanol S177845 0.993 367.2
  Phenylethanolamine A 1346746-81-3 C19H24N2O4 Methanol S148439 0.998 344.2
  Mabuterol 56341-08-3 C13H18ClF3N2O Methanol S177845 0.999 310.1
  Salbutamol 18559-94-9 C13H21NO3 Methanol S177845 0.994 239.2
  Zilpaterol 117827-79-9 C14H19N3O2 Methanol S177845 0.961 261.2
  Cimaterol 54239-37-1 C12H17N3O Methanol S172505 0.980 219.1
  Terbutaline 23031-25-6 C12H19NO3 Methanol S177845 0.999 225.1
  Clenbuterol 37148-27-9 C12H18Cl2N2O Methanol S177845 0.988 276.1
  Cimbuterol 54239-39-3 C13H19N3O Methanol S096141 0.999 233.2
  Brombuterol 41937-02-4 C12H18Br2N2O Methanol S134561 0.994 364.0
  Formoterol 73573-87-2 C19H24N2O4 Methanol S146953 0.999 344.2
Amphenicol
  Chloramphenicol 56-75-7 C11H12Cl2N2O5 Methanol S145561 0.998 322.0
Tranquilizer
  Chlorpromazine 50-53-3 C17H19ClN2S Methanol S167751 0.980 318.1
  Methaqualone 72-44-6 C16H14N2O Methanol ALT028069 0.999 250.1
  Xylazine 7361-61-7 C12H16N2S Methanol S159793 0.990 220.1
  Estazolam 29975-16-4 C16H11ClN4 Methanol S119943 0.999 294.1
  Midazolam 59467-70-8 C18H13ClFN3 Methanol S119943 0.994 325.8
  Triazolam 28911-01-5 C17H12Cl2N4 Methanol S119943 0.992 342.0
  Alprazolam 28981-97-7 C17H13ClN4 Methanol S119943 0.999 308.1
  Diazepam 439-14-5 C16H13ClN2O Methanol S119943 0.999 284.1
  Nitrazepam 146-22-5 C15H11N3O3 Methanol S119943 0.999 281.1
  Oxazepam 604-75-1 C15H11ClN2O2 Methanol S119943 0.996 286.1
  Clonazepam 1622-61-3 C15H10ClN3O3 Methanol S119943 0.999 315.0
  Lorazepam 846-49-1 C15H10Cl2N2O2 Methanol S119943 0.999 320.0
  Phenobarbital 50-06-6 C12H12N2O3 Methanol S142179 0.999 232.1
  Barbital 57-44-3 C8H12N2O3 Methanol S142179 0.999 184.1
  Amobarbital 57-43-2 C11H18N2O3 Methanol S142179 0.999 226.1
  Secobarbital 76-73-3 C12H18N2O3 Methanol S142179 0.999 238.1
Fluoroquinolone
  Norfloxacin 70458-96-7 C16H18FN3O3 Methanol S117199 0.999 319.1
  Pefloxacin 70458-92-3 C17H20FN3O3 Methanol S117199 0.987 333.2
  Lomefloxacin 98079-51-7 C17H19F2N3O3 Methanol S117199 0.904 351.1
  Ofloxacin 82419-36-1 C18H20FN3O4 Methanol S117199 0.995 361.1
Nitroimidazole
  Dimetridazole 551-92-8 C5H7N3O2 Methanol S169555 0.999 141.1
  Dimetridazole-2-hydroxy 936-05-0 C5H7N3O3 Methanol S169555 0.980 157.1
  Metronidazole-hydroxy 4812-40-2 C6H9N3O4 Methanol S169555 0.996 187.1
  Metronidazole 443-48-1 C6H9N3O3 Methanol S169555 0.999 171.1
  Ronidazole 7681-76-7 C6H8N4O4 Methanol S169555 0.990 200.1
  Ipronidazole 14885-29-1 C7H11N3O2 Methanol S094613 0.999 169.1
  Tinidazole 19387-91-8 C8H13N3O4S Methanol S143801 0.999 247.1
Quinoxaline
  2-Quinoxaline-carboxylic acid (2-QCA) 879-65-2 C9H6N2O2 Methanol S153963 0.950 174.0
  3-Methyl-2-quinoxaline-carboxylic acid (MQCA) 74003-63-7 C10H8N2O2 Methanol S160521 0.999 188.1
  Carbadox 6804-07-5 C11H10N4O4 Methanol/DMSO (3∶1) S095207 0.972 262.1
Others
  Dapsone 80-08-0 C12H12N2O2S Acetonitrile S125593 0.994 248.1
  Leucomalachite green 129-73-7 C23H26N2 Methanol S167117 0.994 330.2
  Malachite green 569-64-2 C23H25ClN2 Methanol S167117 0.981 364.9
  Clonidine 4205-90-7 C9H9Cl2N3 Methanol S146723 0.998 229.0
  Cyproheptadine 129-03-3 C21H21N Methanol S149739 0.998 287.4
  Carbofuran 1563-66-2 C12H15NO3 Acetonitrile 2250832 0.999 221.1
  Chlordimeform 6164-98-3 C10H13ClN2 Methanol S168431 0.989 196.1
  Fipronil 120068-37-3 C12H4Cl2F6N4OS Acetonitrile S163547 0.995 435.9
Internal standard (IS)
  Cimbuterol-d9 1246819-04-4 C13H10D9N3O Methanol G0065083 0.977 242.2
  Zilpaterol-d7 1217818-36-4 C14H12D7N3O2 Methanol G0088143 > 0.98 268.2
  2-QCA-d4 2244217-89-6 C9H2D4N2O2 Methanol H0095896 0.980 178.1
  Metronidazole-hydroxy-d2 2196180-19-3 C6H7D2N3O4 Methanol H3000662 0.980 189.1
  Pefloxacin-d5 1228182-51-1 C17H15D5FN3O3 Methanol F0058438 0.996 338.2
  Dapsone-d8 557794-38-4 C12H4D8N2O2S Methanol D0054643 1.000 256.1
  Carbofuran-d3 1007459-98-4 C12H12D3NO3 Methanol E0066530 0.998 224.1
  Fipronil-13C415N2 - C813C4H4Cl2F6N215N2OS Methanol A0069672 1.000 443.1
  Leucomalachite green-d6 1173021-13-0 C23H20D6N2 Acetonitrile G0093712 0.998 336.3
  Malachite green-d5 - C23H20D5ClN2 Acetonitrile G0093712 0.596 369.9
), ArticleFig(id=1194703708618465915, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1193259087325524515, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
CompoundPrecursor ion (m/z)Product ion (m/z)Retention time/minFragmentor/VCollision energy/VPolarityIS
β-Agonist
  Clorprenaline 214.1 196.0*/153.9 5.97 380 8/12 +
  Tulobuterol 228.1 154.0*/119.1 7.00 380 12/32 +
  Ractopamine 302.2 284.2*/164.1 5.81 380 8/12 +
  Bambuterol 368.2 72.0*/46.1 8.29 380 57/25 +
  Phenylethanolamine A 345.2 327.2*/150.2 11.61 380 13/21 +
  Mabuterol 311.0 293.0/237.0* 8.68 380 9/17 +
  Salbutamol 240.2 166.1/148.1* 3.64 380 4/16 + Zilpaterol-d7
  Zilpaterol 262.2 202.0/185.1* 3.62 380 21/25 + Zilpaterol-d7
  Cimaterol 220.1 202.1*/160.1 3.80 380 4/12 + Cimbuterol-d9
  Terbutaline 226.1 170.1/152.1* 3.64 380 8/12 + Cimbuterol-d9
  Clenbuterol 277.1 259.1/203.0* 7.10 380 4/12 + Cimbuterol-d9
  Cimbuterol 234.0 160.0*/143.0 4.35 380 13/29 + Cimbuterol-d9
  Brombuterol 365.0 290.9*/212.0 8.09 380 17/33 + Cimbuterol-d9
  Formoterol 345.2 149.1*/121.3 6.98 380 21/33 + Cimbuterol-d9
Amphenicol
  Chloramphenicol 321.0 257.0/152.1* 9.61 380 16/14 -
Tranquilizer
  Chlorpromazine 319.1 86.1/58.2* 13.94 380 16/44 +
  Methaqualone 251.1 132.1/91.0* 14.16 380 37/49 +
  Xylazine 221.1 90.0*/72.0 6.94 380 40/40 +
  Estazolam 295.1 267.0*/192.0 13.55 380 25/23 +
  Midazolam 326.1 291.1*/223.2 10.83 380 29/45 +
  Triazolam 343.1 314.9/308.0* 14.01 380 25/28 +
  Alprazolam 309.1 281.3/205.2* 13.88 380 29/53 +
  Diazepam 285.1 222.1/193.1* 15.23 380 33/37 +
  Nitrazepam 282.1 207.2*/180.2 13.58 380 37/41 +
  Oxazepam 287.1 241.0*/162.9 13.51 380 25/45 +
  Clonazepam 316.0 240.9/213.8* 13.89 380 34/38 +
  Lorazepam 321.0 302.9/275.0* 13.79 380 21/25 +
  Barbital 183.2 140.1*/84.9 5.92 380 9/9 -
  Secobarbital 237.2 194.2*/84.9 13.71 380 9/9 -
  Phenobarbital 231.0 188.1*/84.9 9.51 380 9/9 -
  Amobarbital 225.2 182.2*/84.9 13.02 380 13/13 -
Fluoroquinolone
  Norfloxacin 320.1 302.1*/231.1 5.32 380 25/40 + Pefloxacin-d5
  Pefloxacin 334.2 316.3*/290.1 5.47 380 21/28 + Pefloxacin-d5
  Lomefloxacin 352.2 334.0/265.0* 5.86 380 20/25 + Pefloxacin-d5
  Ofloxacin 362.2 318.2*/261.1 5.38 380 20/40 + Pefloxacin-d5
Nitroimidazole
  Dimetridazole 142.1 96.1*/81.1 5.22 380 16/28 + Metronidazole-hydroxy-d2
  Dimetridazole-2-hydroxy 158.1 140.0/55.2* 4.25 380 8/20 + Metronidazole-hydroxy-d2
  Metronidazole-hydroxy 188.1 126.1*/123.1 3.76 380 16/8 + Metronidazole-hydroxy-d2
  Metronidazole 172.1 128.0*/82.1 4.31 380 12/24 + Metronidazole-hydroxy-d2
  Ronidazole 201.1 140.1*/55.2 4.69 380 8/25 + Metronidazole-hydroxy-d2
  Ipronidazole 170.1 124.0*/109.0 9.62 380 16/26 + Metronidazole-hydroxy-d2
  Tinidazole 248.1 121.0/29.2* 6.00 380 17/21 +
Quinoxaline
  2-QCA 175.0 128.9/102.0* 5.22 380 16/40 + 2-QCA-d4
  MQCA 189.1 145.0*/143.0 5.24 380 12/16 + 2-QCA-d4
  Carbadox 263.1 231.2*/130.1 5.43 380 13/21 + 2-QCA-d4
Others
  Dapsone 249.1 156.0/92.0* 7.76 380 10/28 + Dapsone-d8
  Leucomalachite green 331.2 316.2/239.2* 17.57 380 20/28 + Leucomalachite green-d6
  Malachite green 329.2 313.1*/284.1 14.66 380 41/65 + Malachite green-d5
  Clonidine 230.0 133.1/74.2* 4.55 380 53/73 +
  Cyproheptadine 288.2 215.1/96.2* 13.34 380 65/25 +
  Carbofuran 222.1 165.1*/123.0 13.62 380 13/25 + Carbofuran-d3
  Chlordimeform 197.1 125.0/117.1* 6.55 380 33/29 +
  Fipronil 434.9 278.0/250.0* 16.16 380 37/33 - Fipronil-13C415N2
IS
  Cimbuterol-d9 243.2 160.9 4.35 380 17 +
  Zilpaterol-d7 269.0 202.9 3.62 380 21 +
  2-QCA-d4 179.0 132.9 5.22 380 21 +
  Metronidazole-hydroxy-d2 190.1 127.9 3.76 380 17 +
  Pefloxacin-d5 339.2 321.1 5.47 380 25 +
  Dapsone-d8 257.4 159.9 7.76 380 17 +
  Carbofuran-d3 225.1 164.8 13.62 380 13 +
  Fipronil-13C415N2 441.0 251.8 16.16 380 29 -
  Leucomalachite green-d6 337.3 240.1 17.57 380 37 +
  Malachite green-d5 334.2 318.2 14.66 380 41 +
), ArticleFig(id=1194703708681380477, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1193259087325524515, language=CN, label=Table 2, caption=

Detailed MS/MS parameters of 53 analytes. *Quantitative ion

, figureFileSmall=null, figureFileBig=null, tableContent=
CompoundPrecursor ion (m/z)Product ion (m/z)Retention time/minFragmentor/VCollision energy/VPolarityIS
β-Agonist
  Clorprenaline 214.1 196.0*/153.9 5.97 380 8/12 +
  Tulobuterol 228.1 154.0*/119.1 7.00 380 12/32 +
  Ractopamine 302.2 284.2*/164.1 5.81 380 8/12 +
  Bambuterol 368.2 72.0*/46.1 8.29 380 57/25 +
  Phenylethanolamine A 345.2 327.2*/150.2 11.61 380 13/21 +
  Mabuterol 311.0 293.0/237.0* 8.68 380 9/17 +
  Salbutamol 240.2 166.1/148.1* 3.64 380 4/16 + Zilpaterol-d7
  Zilpaterol 262.2 202.0/185.1* 3.62 380 21/25 + Zilpaterol-d7
  Cimaterol 220.1 202.1*/160.1 3.80 380 4/12 + Cimbuterol-d9
  Terbutaline 226.1 170.1/152.1* 3.64 380 8/12 + Cimbuterol-d9
  Clenbuterol 277.1 259.1/203.0* 7.10 380 4/12 + Cimbuterol-d9
  Cimbuterol 234.0 160.0*/143.0 4.35 380 13/29 + Cimbuterol-d9
  Brombuterol 365.0 290.9*/212.0 8.09 380 17/33 + Cimbuterol-d9
  Formoterol 345.2 149.1*/121.3 6.98 380 21/33 + Cimbuterol-d9
Amphenicol
  Chloramphenicol 321.0 257.0/152.1* 9.61 380 16/14 -
Tranquilizer
  Chlorpromazine 319.1 86.1/58.2* 13.94 380 16/44 +
  Methaqualone 251.1 132.1/91.0* 14.16 380 37/49 +
  Xylazine 221.1 90.0*/72.0 6.94 380 40/40 +
  Estazolam 295.1 267.0*/192.0 13.55 380 25/23 +
  Midazolam 326.1 291.1*/223.2 10.83 380 29/45 +
  Triazolam 343.1 314.9/308.0* 14.01 380 25/28 +
  Alprazolam 309.1 281.3/205.2* 13.88 380 29/53 +
  Diazepam 285.1 222.1/193.1* 15.23 380 33/37 +
  Nitrazepam 282.1 207.2*/180.2 13.58 380 37/41 +
  Oxazepam 287.1 241.0*/162.9 13.51 380 25/45 +
  Clonazepam 316.0 240.9/213.8* 13.89 380 34/38 +
  Lorazepam 321.0 302.9/275.0* 13.79 380 21/25 +
  Barbital 183.2 140.1*/84.9 5.92 380 9/9 -
  Secobarbital 237.2 194.2*/84.9 13.71 380 9/9 -
  Phenobarbital 231.0 188.1*/84.9 9.51 380 9/9 -
  Amobarbital 225.2 182.2*/84.9 13.02 380 13/13 -
Fluoroquinolone
  Norfloxacin 320.1 302.1*/231.1 5.32 380 25/40 + Pefloxacin-d5
  Pefloxacin 334.2 316.3*/290.1 5.47 380 21/28 + Pefloxacin-d5
  Lomefloxacin 352.2 334.0/265.0* 5.86 380 20/25 + Pefloxacin-d5
  Ofloxacin 362.2 318.2*/261.1 5.38 380 20/40 + Pefloxacin-d5
Nitroimidazole
  Dimetridazole 142.1 96.1*/81.1 5.22 380 16/28 + Metronidazole-hydroxy-d2
  Dimetridazole-2-hydroxy 158.1 140.0/55.2* 4.25 380 8/20 + Metronidazole-hydroxy-d2
  Metronidazole-hydroxy 188.1 126.1*/123.1 3.76 380 16/8 + Metronidazole-hydroxy-d2
  Metronidazole 172.1 128.0*/82.1 4.31 380 12/24 + Metronidazole-hydroxy-d2
  Ronidazole 201.1 140.1*/55.2 4.69 380 8/25 + Metronidazole-hydroxy-d2
  Ipronidazole 170.1 124.0*/109.0 9.62 380 16/26 + Metronidazole-hydroxy-d2
  Tinidazole 248.1 121.0/29.2* 6.00 380 17/21 +
Quinoxaline
  2-QCA 175.0 128.9/102.0* 5.22 380 16/40 + 2-QCA-d4
  MQCA 189.1 145.0*/143.0 5.24 380 12/16 + 2-QCA-d4
  Carbadox 263.1 231.2*/130.1 5.43 380 13/21 + 2-QCA-d4
Others
  Dapsone 249.1 156.0/92.0* 7.76 380 10/28 + Dapsone-d8
  Leucomalachite green 331.2 316.2/239.2* 17.57 380 20/28 + Leucomalachite green-d6
  Malachite green 329.2 313.1*/284.1 14.66 380 41/65 + Malachite green-d5
  Clonidine 230.0 133.1/74.2* 4.55 380 53/73 +
  Cyproheptadine 288.2 215.1/96.2* 13.34 380 65/25 +
  Carbofuran 222.1 165.1*/123.0 13.62 380 13/25 + Carbofuran-d3
  Chlordimeform 197.1 125.0/117.1* 6.55 380 33/29 +
  Fipronil 434.9 278.0/250.0* 16.16 380 37/33 - Fipronil-13C415N2
IS
  Cimbuterol-d9 243.2 160.9 4.35 380 17 +
  Zilpaterol-d7 269.0 202.9 3.62 380 21 +
  2-QCA-d4 179.0 132.9 5.22 380 21 +
  Metronidazole-hydroxy-d2 190.1 127.9 3.76 380 17 +
  Pefloxacin-d5 339.2 321.1 5.47 380 25 +
  Dapsone-d8 257.4 159.9 7.76 380 17 +
  Carbofuran-d3 225.1 164.8 13.62 380 13 +
  Fipronil-13C415N2 441.0 251.8 16.16 380 29 -
  Leucomalachite green-d6 337.3 240.1 17.57 380 37 +
  Malachite green-d5 334.2 318.2 14.66 380 41 +
), ArticleFig(id=1194703708765266559, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1193259087325524515, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
CompoundLOD/μg·kg-1LOQ/μg·kg-1Linear equationLinear range/μg·L-1rME/%
β-Agonist
  Clorprenaline 0.1 0.2 y = 5 841 216.26 x + 87 425.55 0.1-1 0.995 95.64
  Tulobuterol 0.1 0.2 y = 6 027 646.87 x + 18 522.54 0.1-1 1.000 86.96
  Ractopamine 0.1 0.2 y = 2 747 991.54 x + 29 099.74 0.1-1 1.000 66.30
  Bambuterol 0.1 0.2 y = 5 194 463.70 x + 44 581.13 0.1-1 0.998 89.90
  Phenylethanolamine A 0.1 0.2 y = 4 057 591.55 x + 99 910.70 0.1-1 0.998 128.25
  Mabuterol 0.1 0.2 y = 5 193 449.89 x + 48 044.08 0.1-1 0.999 69.61
  Salbutamol 0.1 0.2 y = 13.89 x - 0.53 0.1-1 0.993 73.17
  Zilpaterol 0.1 0.2 y = 3.15 x - 0.27 0.1-1 0.991 65.09
  Cimaterol 0.1 0.2 y = 0.41 x - 0.01 0.1-1 0.995 49.36
  Terbutaline 0.1 0.2 y = 1.19 x - 0.01 0.1-1 0.997 55.38
  Clenbuterol 0.1 0.2 y = 0.88 x + 0.02 0.1-1 0.996 78.58
  Cimbuterol 0.1 0.2 y = 1.26 x + 0.09 0.1-1 0.997 73.32
  Brombuterol 0.1 0.2 y = 0.20 x + 0.01 0.1-1 0.997 62.23
  Formoterol 0.1 0.2 y = 1.48 x + 0.02 0.1-1 0.993 101.37
Amphenicol
  Chloramphenicol 0.1 0.2 y = 95 516.35 x - 14.83 0.1-1 0.999 69.46
Tranquilizer
  Chlorpromazine 0.1 0.2 y = 4 311 198.01 x - 123 375.27 0.1-1 0.998 91.62
  Methaqualone 0.1 0.2 y = 5 181 626.41 x - 67 016.44 0.1-1 0.998 76.57
  Xylazine 0.1 0.2 y = 1 414 153.91 x + 11 363.70 0.1-1 1.000 86.53
  Estazolam 0.1 0.2 y = 1 079 542.68 x + 12 236.56 0.1-1 0.998 116.99
  Midazolam 0.1 0.2 y = 1 694 281.78 x + 2 928.75 0.1-1 0.998 58.64
  Triazolam 0.1 0.2 y = 784 153.47 x - 427.84 0.1-1 0.999 107.84
  Alprazolam 0.1 0.2 y = 722 016.87 x - 7 329.70 0.1-1 0.999 73.13
  Diazepam 0.1 0.2 y = 563 673.41 x - 10 515.61 0.1-1 0.999 81.37
  Nitrazepam 0.1 0.2 y = 75 022.22 x - 1 339.64 0.1-1 0.997 57.22
  Oxazepam 0.1 0.2 y = 374 484.50 x + 7 089.87 0.1-1 0.999 263.27
  Clonazepam 0.1 0.2 y = 51 232.53 x + 520.24 0.1-1 0.996 52.90
  Lorazepam 0.1 0.2 y = 261 090.69 x + 2 415.79 0.1-1 0.997 234.22
  Phenobarbital 50 100 y = 442.00 x + 3 375.35 50-500 0.998 91.27
  Barbital 50 100 y = 349.63 x - 3 857.60 50-500 0.998 63.24
  Amobarbital 50 100 y = 1 200.29 x + 15 337.73 50-500 0.997 85.00
  Secobarbital 50 100 y = 554.73 x - 4 923.25 50-500 0.998 39.30
Fluoroquinolone
  Norfloxacin 0.2 0.4 y = 0.37 x - 0.03 0.2-2 0.993 268.90
  Pefloxacin 0.2 0.4 y = 0.47 x + 0.01 0.2-2 0.999 177.75
  Lomefloxacin 0.2 0.4 y = 0.13 x - 0.00 0.2-2 0.996 60.97
  Ofloxacin 0.2 0.4 y = 0.42 x - 0.01 0.2-2 0.997 111.81
  Nitroimidazole
  Dimetridazole 2 4 y = 0.17 x - 0.04 1-10 0.999 86.52
  Dimetridazole-2-hydroxy 2 4 y = 0.05 x - 0.05 1-10 0.996 36.07
  Metronidazole-hydroxy 2 4 y = 0.09 x + 0.15 1-10 0.995 57.96
  Metronidazole 2 4 y = 0.52 x - 0.08 1-10 0.996 161.30
  Ronidazole 2 4 y = 0.72 x - 0.40 1-10 0.998 142.78
  Ipronidazole 2 4 y = 0.22 x + 0.08 1-10 0.999 78.37
  Tinidazole 2 4 y = 310 695.06 x + 52 015.05 1-10 1.000 91.53
Quinoxaline
  2-QCA 25 50 y = 0.534 x + 0.03 25-250 0.996 112.92
  MQCA 25 50 y = 5.11 x + 0.01 25-250 0.998 120.07
  Carbadox 25 50 y = 35.29 x + 0.40 25-250 0.999 109.83
Others
  Dapsone 0.1 0.2 y = 1.46 x - 0.01 0.1-1 0.997 95.36
  Leucomalachite green 0.1 0.2 y = 0.59 x - 0.06 0.1-1 0.995 108.42
  Malachite green 0.1 0.2 y = 1.46 x - 0.18 0.1-1 0.996 60.44
  Clonidine 0.1 0.2 y = 301 538.77 x - 7 590.75 0.1-1 0.997 76.02
  Cyproheptadine 0.1 0.2 y = 2 368 886.83 x - 24 673.13 0.1-1 0.998 78.51
  Carbofuran 0.1 0.2 y = 0.82 x - 0.00 0.1-1 0.999 49.77
  Chlordimeform 0.1 0.2 y = 1 083 880.45 x + 15 761.62 0.1-1 0.996 84.15
  Fipronil 0.1 0.2 y = 0.86 x - 0.03 0.1-1 1.000 122.19
), ArticleFig(id=1194703708832375425, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1193259087325524515, language=CN, label=Table 3, caption=

The LODs, LOQs, linear equations, ranges, and MEs for 53 analytes

, figureFileSmall=null, figureFileBig=null, tableContent=
CompoundLOD/μg·kg-1LOQ/μg·kg-1Linear equationLinear range/μg·L-1rME/%
β-Agonist
  Clorprenaline 0.1 0.2 y = 5 841 216.26 x + 87 425.55 0.1-1 0.995 95.64
  Tulobuterol 0.1 0.2 y = 6 027 646.87 x + 18 522.54 0.1-1 1.000 86.96
  Ractopamine 0.1 0.2 y = 2 747 991.54 x + 29 099.74 0.1-1 1.000 66.30
  Bambuterol 0.1 0.2 y = 5 194 463.70 x + 44 581.13 0.1-1 0.998 89.90
  Phenylethanolamine A 0.1 0.2 y = 4 057 591.55 x + 99 910.70 0.1-1 0.998 128.25
  Mabuterol 0.1 0.2 y = 5 193 449.89 x + 48 044.08 0.1-1 0.999 69.61
  Salbutamol 0.1 0.2 y = 13.89 x - 0.53 0.1-1 0.993 73.17
  Zilpaterol 0.1 0.2 y = 3.15 x - 0.27 0.1-1 0.991 65.09
  Cimaterol 0.1 0.2 y = 0.41 x - 0.01 0.1-1 0.995 49.36
  Terbutaline 0.1 0.2 y = 1.19 x - 0.01 0.1-1 0.997 55.38
  Clenbuterol 0.1 0.2 y = 0.88 x + 0.02 0.1-1 0.996 78.58
  Cimbuterol 0.1 0.2 y = 1.26 x + 0.09 0.1-1 0.997 73.32
  Brombuterol 0.1 0.2 y = 0.20 x + 0.01 0.1-1 0.997 62.23
  Formoterol 0.1 0.2 y = 1.48 x + 0.02 0.1-1 0.993 101.37
Amphenicol
  Chloramphenicol 0.1 0.2 y = 95 516.35 x - 14.83 0.1-1 0.999 69.46
Tranquilizer
  Chlorpromazine 0.1 0.2 y = 4 311 198.01 x - 123 375.27 0.1-1 0.998 91.62
  Methaqualone 0.1 0.2 y = 5 181 626.41 x - 67 016.44 0.1-1 0.998 76.57
  Xylazine 0.1 0.2 y = 1 414 153.91 x + 11 363.70 0.1-1 1.000 86.53
  Estazolam 0.1 0.2 y = 1 079 542.68 x + 12 236.56 0.1-1 0.998 116.99
  Midazolam 0.1 0.2 y = 1 694 281.78 x + 2 928.75 0.1-1 0.998 58.64
  Triazolam 0.1 0.2 y = 784 153.47 x - 427.84 0.1-1 0.999 107.84
  Alprazolam 0.1 0.2 y = 722 016.87 x - 7 329.70 0.1-1 0.999 73.13
  Diazepam 0.1 0.2 y = 563 673.41 x - 10 515.61 0.1-1 0.999 81.37
  Nitrazepam 0.1 0.2 y = 75 022.22 x - 1 339.64 0.1-1 0.997 57.22
  Oxazepam 0.1 0.2 y = 374 484.50 x + 7 089.87 0.1-1 0.999 263.27
  Clonazepam 0.1 0.2 y = 51 232.53 x + 520.24 0.1-1 0.996 52.90
  Lorazepam 0.1 0.2 y = 261 090.69 x + 2 415.79 0.1-1 0.997 234.22
  Phenobarbital 50 100 y = 442.00 x + 3 375.35 50-500 0.998 91.27
  Barbital 50 100 y = 349.63 x - 3 857.60 50-500 0.998 63.24
  Amobarbital 50 100 y = 1 200.29 x + 15 337.73 50-500 0.997 85.00
  Secobarbital 50 100 y = 554.73 x - 4 923.25 50-500 0.998 39.30
Fluoroquinolone
  Norfloxacin 0.2 0.4 y = 0.37 x - 0.03 0.2-2 0.993 268.90
  Pefloxacin 0.2 0.4 y = 0.47 x + 0.01 0.2-2 0.999 177.75
  Lomefloxacin 0.2 0.4 y = 0.13 x - 0.00 0.2-2 0.996 60.97
  Ofloxacin 0.2 0.4 y = 0.42 x - 0.01 0.2-2 0.997 111.81
  Nitroimidazole
  Dimetridazole 2 4 y = 0.17 x - 0.04 1-10 0.999 86.52
  Dimetridazole-2-hydroxy 2 4 y = 0.05 x - 0.05 1-10 0.996 36.07
  Metronidazole-hydroxy 2 4 y = 0.09 x + 0.15 1-10 0.995 57.96
  Metronidazole 2 4 y = 0.52 x - 0.08 1-10 0.996 161.30
  Ronidazole 2 4 y = 0.72 x - 0.40 1-10 0.998 142.78
  Ipronidazole 2 4 y = 0.22 x + 0.08 1-10 0.999 78.37
  Tinidazole 2 4 y = 310 695.06 x + 52 015.05 1-10 1.000 91.53
Quinoxaline
  2-QCA 25 50 y = 0.534 x + 0.03 25-250 0.996 112.92
  MQCA 25 50 y = 5.11 x + 0.01 25-250 0.998 120.07
  Carbadox 25 50 y = 35.29 x + 0.40 25-250 0.999 109.83
Others
  Dapsone 0.1 0.2 y = 1.46 x - 0.01 0.1-1 0.997 95.36
  Leucomalachite green 0.1 0.2 y = 0.59 x - 0.06 0.1-1 0.995 108.42
  Malachite green 0.1 0.2 y = 1.46 x - 0.18 0.1-1 0.996 60.44
  Clonidine 0.1 0.2 y = 301 538.77 x - 7 590.75 0.1-1 0.997 76.02
  Cyproheptadine 0.1 0.2 y = 2 368 886.83 x - 24 673.13 0.1-1 0.998 78.51
  Carbofuran 0.1 0.2 y = 0.82 x - 0.00 0.1-1 0.999 49.77
  Chlordimeform 0.1 0.2 y = 1 083 880.45 x + 15 761.62 0.1-1 0.996 84.15
  Fipronil 0.1 0.2 y = 0.86 x - 0.03 0.1-1 1.000 122.19
), ArticleFig(id=1194703708983370372, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1193259087325524515, language=EN, label=null, caption=null, figureFileSmall=null, figureFileBig=null, tableContent=
Compound1 LOQ2 LOQ10 LOQ
Recovery/%RSD/%Recovery/%RSD/%Recovery/%RSD/%
β-Agonist
  Clorprenaline 81.65 8.99 83.27 5.52 93.53 6.40
  Tulobuterol 84.69 7.12 86.37 3.26 90.42 2.34
  Ractopamine 74.17 10.29 71.26 8.35 84.82 5.42
  Bambuterol 76.66 9.54 87.41 5.04 98.90 1.99
  Phenylethanolamine A 70.40 6.93 72.93 5.44 92.14 4.17
  Mabuterol 77.92 6.10 87.31 2.51 92.87 2.97
  Salbutamol 101.52 9.87 93.61 9.07 94.50 8.53
  Zilpaterol 114.34 5.21 99.62 5.73 89.48 10.47
  Cimaterol 106.96 7.20 83.02 11.04 92.25 7.08
  Terbutaline 94.65 9.77 89.19 9.41 82.22 8.99
  Clenbuterol 106.31 5.20 116.42 10.44 117.36 7.95
  Cimbuterol 79.27 10.45 86.07 9.81 118.64 7.43
  Brombuterol 102.95 9.44 113.33 11.05 117.89 1.95
  Formoterol 111.92 4.43 105.16 4.67 118.70 3.44
Amphenicol
  Chloramphenicol 85.65 2.32 88.29 2.71 94.70 3.43
Tranquilizer
  Chlorpromazine 70.92 4.22 81.41 3.42 84.73 9.71
  Methaqualone 95.55 8.78 93.92 5.17 96.72 3.60
  Xylazine 76.42 5.38 88.01 3.18 97.89 3.97
  Estazolam 94.54 6.29 93.84 3.96 102.29 6.10
  Midazolam 80.00 7.39 93.12 3.64 102.31 6.14
  Triazolam 92.08 7.38 107.75 2.21 116.78 4.37
  Alprazolam 110.67 8.49 116.83 2.65 118.03 4.62
  Diazepam 97.93 10.26 102.39 6.70 106.23 4.73
  Nitrazepam 74.28 7.48 81.54 8.25 86.06 4.63
  Oxazepam 78.74 8.78 82.45 8.16 93.86 4.92
  Clonazepam 86.37 6.43 81.12 10.44 95.40 8.76
  Lorazepam 80.59 8.15 81.34 7.86 91.48 3.71
  Phenobarbital 83.52 3.85 96.46 5.93 100.19 1.45
  Barbital 93.87 7.54 87.32 5.99 97.23 6.21
  Amobarbital 75.73 4.05 87.45 6.94 94.54 3.05
  Secobarbital 85.78 4.88 86.79 6.58 86.73 5.35
Fluoroquinolone
  Norfloxacin 100.39 5.02 89.32 1.93 84.17 4.61
  Pefloxacin 86.99 2.91 94.55 4.22 95.97 3.97
  Lomefloxacin 109.14 4.29 104.26 2.36 104.11 3.60
  Ofloxacin 112.11 4.70 101.32 2.14 96.25 7.12
Nitroimidazole
  Dimetridazole 104.62 8.29 89.95 1.55 94.29 9.77
  Dimetridazole-2-hydroxy 113.47 8.58 99.60 5.50 95.19 12.07
  Metronidazole-hydroxy 97.53 7.23 101.34 4.77 97.18 5.16
  Metronidazole 86.93 10.67 90.35 4.39 91.06 7.65
  Ronidazole 113.83 7.29 92.73 4.15 94.21 9.84
  Ipronidazole 92.84 8.01 81.48 8.47 86.78 10.11
  Tinidazole 78.74 8.11 88.82 5.84 101.48 5.16
Quinoxaline
  2-QCA 84.68 10.03 100.67 8.45 98.38 1.21
  MQCA 109.14 6.24 100.36 7.68 98.07 0.69
  Carbadox 104.18 9.14 101.76 6.11 99.31 6.42
Others
  Dapsone 89.94 4.16 97.97 3.55 96.88 6.76
  Leucomalachite green 105.46 10.96 80.71 8.69 94.35 3.47
  Malachite green 103.38 8.54 80.43 2.38 71.39 1.33
  Clonidine 95.29 9.74 86.11 5.31 87.89 8.25
  Cyproheptadine 74.09 3.94 71.91 6.14 83.47 2.67
  Carbofuran 88.18 4.05 93.99 5.05 98.36 2.23
  Chlordimeform 78.45 5.35 80.89 5.82 101.92 2.03
  Fipronil 96.04 4.31 90.39 4.15 91.07 6.02
), ArticleFig(id=1194703709197279879, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1193259087325524515, language=CN, label=Table 4, caption=

Recoveries and RSDs for 53 compounds at three spiked levels

, figureFileSmall=null, figureFileBig=null, tableContent=
Compound1 LOQ2 LOQ10 LOQ
Recovery/%RSD/%Recovery/%RSD/%Recovery/%RSD/%
β-Agonist
  Clorprenaline 81.65 8.99 83.27 5.52 93.53 6.40
  Tulobuterol 84.69 7.12 86.37 3.26 90.42 2.34
  Ractopamine 74.17 10.29 71.26 8.35 84.82 5.42
  Bambuterol 76.66 9.54 87.41 5.04 98.90 1.99
  Phenylethanolamine A 70.40 6.93 72.93 5.44 92.14 4.17
  Mabuterol 77.92 6.10 87.31 2.51 92.87 2.97
  Salbutamol 101.52 9.87 93.61 9.07 94.50 8.53
  Zilpaterol 114.34 5.21 99.62 5.73 89.48 10.47
  Cimaterol 106.96 7.20 83.02 11.04 92.25 7.08
  Terbutaline 94.65 9.77 89.19 9.41 82.22 8.99
  Clenbuterol 106.31 5.20 116.42 10.44 117.36 7.95
  Cimbuterol 79.27 10.45 86.07 9.81 118.64 7.43
  Brombuterol 102.95 9.44 113.33 11.05 117.89 1.95
  Formoterol 111.92 4.43 105.16 4.67 118.70 3.44
Amphenicol
  Chloramphenicol 85.65 2.32 88.29 2.71 94.70 3.43
Tranquilizer
  Chlorpromazine 70.92 4.22 81.41 3.42 84.73 9.71
  Methaqualone 95.55 8.78 93.92 5.17 96.72 3.60
  Xylazine 76.42 5.38 88.01 3.18 97.89 3.97
  Estazolam 94.54 6.29 93.84 3.96 102.29 6.10
  Midazolam 80.00 7.39 93.12 3.64 102.31 6.14
  Triazolam 92.08 7.38 107.75 2.21 116.78 4.37
  Alprazolam 110.67 8.49 116.83 2.65 118.03 4.62
  Diazepam 97.93 10.26 102.39 6.70 106.23 4.73
  Nitrazepam 74.28 7.48 81.54 8.25 86.06 4.63
  Oxazepam 78.74 8.78 82.45 8.16 93.86 4.92
  Clonazepam 86.37 6.43 81.12 10.44 95.40 8.76
  Lorazepam 80.59 8.15 81.34 7.86 91.48 3.71
  Phenobarbital 83.52 3.85 96.46 5.93 100.19 1.45
  Barbital 93.87 7.54 87.32 5.99 97.23 6.21
  Amobarbital 75.73 4.05 87.45 6.94 94.54 3.05
  Secobarbital 85.78 4.88 86.79 6.58 86.73 5.35
Fluoroquinolone
  Norfloxacin 100.39 5.02 89.32 1.93 84.17 4.61
  Pefloxacin 86.99 2.91 94.55 4.22 95.97 3.97
  Lomefloxacin 109.14 4.29 104.26 2.36 104.11 3.60
  Ofloxacin 112.11 4.70 101.32 2.14 96.25 7.12
Nitroimidazole
  Dimetridazole 104.62 8.29 89.95 1.55 94.29 9.77
  Dimetridazole-2-hydroxy 113.47 8.58 99.60 5.50 95.19 12.07
  Metronidazole-hydroxy 97.53 7.23 101.34 4.77 97.18 5.16
  Metronidazole 86.93 10.67 90.35 4.39 91.06 7.65
  Ronidazole 113.83 7.29 92.73 4.15 94.21 9.84
  Ipronidazole 92.84 8.01 81.48 8.47 86.78 10.11
  Tinidazole 78.74 8.11 88.82 5.84 101.48 5.16
Quinoxaline
  2-QCA 84.68 10.03 100.67 8.45 98.38 1.21
  MQCA 109.14 6.24 100.36 7.68 98.07 0.69
  Carbadox 104.18 9.14 101.76 6.11 99.31 6.42
Others
  Dapsone 89.94 4.16 97.97 3.55 96.88 6.76
  Leucomalachite green 105.46 10.96 80.71 8.69 94.35 3.47
  Malachite green 103.38 8.54 80.43 2.38 71.39 1.33
  Clonidine 95.29 9.74 86.11 5.31 87.89 8.25
  Cyproheptadine 74.09 3.94 71.91 6.14 83.47 2.67
  Carbofuran 88.18 4.05 93.99 5.05 98.36 2.23
  Chlordimeform 78.45 5.35 80.89 5.82 101.92 2.03
  Fipronil 96.04 4.31 90.39 4.15 91.07 6.02
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盐析辅助液液萃取-超高效液相色谱串联质谱法测定山羊角中53种禁用兽药残留
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劳柏豪 1, 2 , 孙健 2, * , 张静娴 2 , 于泓 2 , 冉莹瑛 2 , 黄帆 2 , 季申 1, 2 , 胡青 1, 2, *
药学学报 | 研究论文 2025,60(3): 791-800
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药学学报 | 研究论文 2025, 60(3): 791-800
盐析辅助液液萃取-超高效液相色谱串联质谱法测定山羊角中53种禁用兽药残留
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劳柏豪1, 2, 孙健2, * , 张静娴2, 于泓2, 冉莹瑛2, 黄帆2, 季申1, 2, 胡青1, 2, *
作者信息
  • 1.上海中医药大学中药学院, 上海 201203
  • 2.上海市食品药品检验研究院, 国家药品监督管理局中药质量控制重点实验室, 上海 201203

通讯作者:

*孙健, Tel: 18001678040, E-mail:
胡青, Tel: 18001677896, E-mail:
Determination of 53 prohibited veterinary drug residues in goat horn by salting-out assisted liquid-liquid extraction combined with UHPLC-MS/MS
Bai-hao LAO1, 2, Jian SUN2, * , Jing-xian ZHANG2, Hong YU2, Ying-ying RAN2, Fan HUANG2, Shen JI1, 2, Qing HU1, 2, *
Affiliations
  • 1. School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
  • 2. National Medical Products Administration Key Laboratory for Quality Control of Traditional Chinese Medicine, Shanghai Institute for Food and Drug Control, Shanghai 201203, China
出版时间: 2025-03-12 doi: 10.16438/j.0513-4870.2024-0995
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建立了UHPLC-MS/MS测定山羊角中53种禁用兽药残留的检测方法, 包括16种镇静剂类、14种β-受体激动剂类、氯霉素、4种氟喹诺酮类、7种硝基咪唑类、3种喹噁啉类化合物、8种其他类化合物。采用盐析辅助液液萃取样品, Zorbax Eclipse Plus C18色谱柱(1.8 μm, 3.0 mm × 150 mm, Agilent), 以0.1%甲酸溶液-乙腈为流动相, 梯度洗脱, 在电喷雾离子化正负离子模式下, 以多反应监测方式(MRM) 检测。53种待测物在各自浓度范围内均成良好线性关系, 相关系数均在0.99以上; 三水平平均加样回收率为70.4%~118.7%, 相对标准偏差(RSD) 为0.69%~12.07%, 检出限为0.1~50 μg·kg-1, 定量限为0.2~100 μg·kg-1。本方法已应用于实际样品的测定。

山羊角  /  禁用兽药残留  /  盐析辅助液液萃取  /  超高效液相色谱串联三重四极杆质谱

A detection method using UHPLC-MS/MS was established for the determination of 53 prohibited veterinary drug residues in goat horns, including 16 tranquilizers, 14 β-agonists, chloramphenicol, 4 fluoroquinolones, 7 nitroimidazoles, 3 quinoxalines, and 8 other compounds. Samples were extracted using salting-out assisted liquid-liquid extraction (SALLE). A Zorbax Eclipse Plus C18 column (1.8 μm, 3.0 mm × 150 mm, Agilent) was used with 0.1% formic acid solution-acetonitrile as the mobile phase for gradient elution. Detection was performed in positive and negative electrospray ionization modes using multiple reaction monitoring (MRM). All 53 analytes showed good linearity within their respective concentration ranges, with correlation coefficients above 0.99. The average recoveries at three spiked levels ranged from 70.4% to 118.7%, with relative standard deviations (RSDs) ranging from 0.69% to 12.07%. The limits of detection (LODs) ranged from 0.1 to 50 μg·kg-1, and the limits of quantitation (LOQs) ranged from 0.2 to 100 μg·kg-1. This method has been applied to the determination of real samples.

goat horn  /  prohibited veterinary drug residue  /  salting-out assisted liquid-liquid extraction  /  UHPLC-MS/MS
劳柏豪, 孙健, 张静娴, 于泓, 冉莹瑛, 黄帆, 季申, 胡青. 盐析辅助液液萃取-超高效液相色谱串联质谱法测定山羊角中53种禁用兽药残留. 药学学报, 2025 , 60 (3) : 791 -800 . DOI: 10.16438/j.0513-4870.2024-0995
Bai-hao LAO, Jian SUN, Jing-xian ZHANG, Hong YU, Ying-ying RAN, Fan HUANG, Shen JI, Qing HU. Determination of 53 prohibited veterinary drug residues in goat horn by salting-out assisted liquid-liquid extraction combined with UHPLC-MS/MS[J]. Acta Pharmaceutica Sinica, 2025 , 60 (3) : 791 -800 . DOI: 10.16438/j.0513-4870.2024-0995
兽药是用于预防、治疗或诊断动物疾病或有目的地调节动物生理功能的药物[1], 被广泛用于畜牧业和农业, 以实现增产增效。在动物使用兽药或食用混有兽药的饲料后, 兽药大多可通过尿液和粪便排出体外, 少数会以原型结构或代谢产物的形式贮存于动物细胞、组织、器官[2, 3]。目前, 兽药残留问题引起了许多国家和组织的关注, 我国[4]及美国[5]、日本[6]、欧盟[7]、国际食品法典委员会(CAC) [8]等已制订了兽药最大残留限量。
值得注意的是, 部分高安全风险品种, 已被证实具有致癌、致畸、致突变等危害[9-11], 已在食品动物养殖过程中禁用。农业农村部第250号公告规定了食品动物中21种(类) 禁止使用的药品及其化合物; 第2292号公告规定在食品动物中停止使用洛美沙星、培氟沙星、氧氟沙星、诺氟沙星4种兽药; 第2428号公告停止硫酸黏菌素用于动物促生长; 第2583号公告禁止非泼罗尼及相关制剂用于食品动物; 第2638号公告规定在食品动物中停止使用喹乙醇、氨苯胂酸、洛克沙胂3种兽药。另外, 农业农村部第176号和第1519号公告对饲料和动物饮用水中禁止使用的兽药作出了明确规定; GB 31650-2019中规定了氯丙嗪等9种允许作治疗用, 但不得在动物性食品中检出的兽药。
已有文献针对食品中禁用兽药残留, 按类别开发了各种检测方法, 如镇静剂[12, 13]β-受体激动剂[14, 15]、喹诺酮类[16, 17]、硝基咪唑类[18]、喹噁啉类[19, 20]; 亦有文献报道了食品中多类别禁用兽药的高通量检测方法[21-24]
与动物源性食品类似, 动物源性中药也存在兽药残留的安全问题, 但尚未得到重视。本课题组前期分别对鸡内金[25]、熊胆粉[26]的兽药残留进行检测, 发现这些中药存在兽药残留安全风险, 特别是禁用兽药检出率较高。因此, 动物源性中药中禁用兽药的监管和检测是亟待解决的问题。
与动物源性食品不同的是, 动物源性中药多为干基, 水分、脂肪含量较低。本文的研究对象为传统中药山羊角, 主要来源于家养山羊(Capra hircus Linnaeus) 的角, 最早记载于《神农本草经》[27], 主要成分为蛋白质类[28]、肽类、核苷类[29]、无机元素类等。根据现代药理学研究, 山羊角具有促凝血、镇静、解热等药理活性[30]。山羊在中国大量养殖, 2018年山羊现存数量达1.357 5亿只[31], 山羊的养殖不可避免地需要使用兽药来调节生长发育、预防和治疗疾病。
基于山羊角的基质成分特点, 本文采用盐析辅助液液萃取前处理, 结合UHPLC/MS/MS方法检测53种禁用兽药, 包括16种镇静剂类、14种β-受体激动剂类、氯霉素、4种氟喹诺酮类、7种硝基咪唑类、3种喹噁啉类及8种其他类化合物。
仪器与试剂  1290/6495型超高效液相色谱串联三重四极杆质谱仪(美国Agilent公司); Zorbax Eclipse Plus C18色谱柱(1.8 μm, 3.0 mm × 150 mm, Agilent)。待测物对照品均购于天津阿尔塔科技有限公司, 内标对照品均购于曼哈格(上海) 生物科技有限公司, 批号、纯度等信息见表 1。乙腈、甲醇为质谱级试剂, 购于北京百灵威科技有限公司; 甲酸为质谱级试剂, 购于美国赛默飞世尔科技有限公司; 甲酸铵为色谱级试剂, 购于西格玛奥德里奇(上海) 贸易有限公司; NaCl、Na2SO4均为分析纯, 购于国药集团化学试剂有限公司。27批山羊角样品中, 样品1~19由上海凯宝药业股份有限公司提供, 产地为内蒙古; 样品20~27由上海康桥中药饮片有限公司提供, 产地分别为山东和浙江。
色谱和质谱条件  Zorbax Eclipse Plus C18色谱柱(1.8 μm, 3.0 mm × 150 mm, Agilent); 柱温为40 ℃, 流速为0.5 mL·min-1, 进样量10 μL。流动相: A为0.1%甲酸(含5 mmol·L-1甲酸铵) 溶液, B为乙腈; 梯度条件如下: 0~0.5 min, 2% B; 0.5~1.8 min, 2%~15% B; 1.8~3.5 min, 15%~20% B; 3.5~6 min, 20%~25% B; 6~7 min, 25%~30% B; 7~11 min, 30%~35% B; 11~16 min, 35%~100% B; 16~26 min, 100% B。
电喷雾离子化(ESI) 正负离子模式; 干燥气(N2) 流速13 L·min-1, 温度210 ℃; 雾化气(N2) 0.24 MPa; 鞘气(N2) 流速12 L·min-1, 温度380 ℃; 毛细管电压正离子为3.5 kV, 负离子为4.0 kV。采用多反应监测方式(MRM) 检测, 监测离子、碰撞能量等参数见表 2
对照品溶液制备方法
标准储备溶液  将53种化合物和内标分别溶解在适当的溶剂中, 制备成浓度为100 μg·mL-1的溶液。
混合中间标准溶液  用15%乙腈溶液稀释上述标准储备溶液, 制备成混合中间标准溶液, 其中β-受体激动剂、氯霉素、镇静剂和其他类别的浓度为10 ng·mL-1; 氟喹诺酮类浓度为20 ng·mL-1; 硝基咪唑类浓度为200 ng·mL-1; 喹噁啉类浓度为2 500 ng·mL-1; 巴比妥类浓度为5 000 ng·mL-1。用15%乙腈溶液稀释内标标准储备溶液, 制备了混合中间内标溶液, 其中氨苯砜-d8、齐帕特罗-d7、西布特罗-d9、克百威-d3、氟虫腈-13C415N2、孔雀石绿-d5和隐色孔雀石绿-d6的浓度为10 ng·mL-1; 培氟沙星-d5的浓度为20 ng·mL-1; 羟基甲硝唑-d2的浓度为200 ng·mL-1; 2-QCA-d4的浓度为2 500 ng·mL-1
标准曲线工作溶液  取空白山羊角样品粉末(未检出53种禁用兽药) 0.5 g, 精密称定, 置于50 mL聚苯乙烯具塞离心管中, 同供试品溶液制备方法制成空白基质溶液。精密吸取2、4、10、15和20 μL混合中间标准溶液和10 μL混合中间内标溶液, 用空白基质溶液定容至200 μL。
供试品溶液制备方法  取山羊角样品适量, 研细, 准确称取0.5 g, 置于50 mL聚苯乙烯具塞离心管中, 加入50 μL混合中间内标溶液, 加水10 mL, 涡旋使充分浸润, 加入1%甲酸乙腈溶液15 mL, 涡旋使其混匀, 置振荡器上剧烈振荡(每分钟500次) 10 min。将NaCl∶Na2SO4 (1∶4) 混合粉末5 g加入离心管中, 再置振荡器上剧烈振荡(每分钟500次) 3 min, 离心5 min, 使溶液分层。吸取上清液3 mL, 在40 ℃水浴下浓缩至干, 精密加0.2 mL 15%乙腈溶液, 涡旋1 min, 混匀, 转速离心(15 000 r·min-1) 2 min, 取上清液, 即得。
系统适用性试验  取最低浓度水平的标准曲线工作溶液, 进样测定, 按上述条件测定的MRM色谱峰的信噪比均应大于10∶1。
方法学验证
线性关系  取标准曲线工作溶液进样测定, 齐帕特罗-d7作为沙丁胺醇和齐帕特罗的内标; 西布特罗-d9作为西马特罗、特布他林、克仑特罗、西布特罗、溴布特罗和福莫特罗的内标; 培氟沙星-d5作为氟喹诺酮类的内标; 羟基甲硝唑-d2作为二甲硝咪唑、2-羟基二甲硝咪唑、羟基甲硝唑、甲硝唑、罗硝唑和异丙硝唑的内标; 2-QCA-d4作为喹噁啉类的内标; 氨苯砜-d8、克百威-d3、氟虫腈-13C415N2、孔雀石绿-d5和隐色孔雀石绿-d6分别作为氨苯砜、克百威、氟虫腈、孔雀石绿和隐色孔雀石绿的内标; 其余化合物以外标法定量, 绘制标准曲线。
专属性  通过检测不含53种兽药的空白样品来评估该方法的选择性。
基质效应  样品的基质成分可能会干扰目标化合物的电离效率。为了评价基质效应(ME), 制备了空白基质匹配标准曲线和溶剂标准曲线, 以ME = (空白基质匹配标准曲线斜率/溶剂标准曲线斜率) × 100%的值来表示基质效应的大小。
检测限  定量限(LOQ) 是准确度和精确度均可接受的最低加样水平。检出限(LOD) 是能从背景噪声中检测到信号的最低加样水平(S/N = 3, 且相对离子丰度比符合要求)。
准确度  取样品, 分别添加低(定量限)、中(2倍定量限)、高(10倍定量限) 3个水平的对照品溶液, 每个水平做6个平行样, 共18份, 按上述供试品溶液制备方法和色谱质谱条件进行分析, 计算回收率。
重复性  取同一批供试品溶液, 按准确度加样平行制备6份供试品溶液, 按色谱和质谱条件进行测定, 计算重复性RSD。
稳定性  取同一水平加样溶液, 在室温下于24 h内每间隔4 h进样测定, 共进样6次, 计算稳定性RSD。
空白基质匹配标准曲线在各自的浓度范围内表现出良好的线性, r值均≥0.99, 线性范围及相关系数见表 3
空白基质色谱图在目标化合物的保留时间处, 均未检测到干扰峰。
53种化合物的ME值为36.07%~268.90%。其中30种化合物的ME值为70%~130%, 基质效应较小; 17种化合物呈现出基质抑制作用; 6种化合物呈现出基质增强作用, 结果见表 3
53种化合物的检出限(LOD) 为0.1~50 μg·kg-1, 定量限为(LOQ) 为0.2~100 μg·kg-1, 结果见表 3
根据CAC/GL 71-2009《与食用动物的兽药使用有关的国家食品安全保障监管方案的设计与执行指南》[32]要求, 当兽药残留水平小于1 μg·kg-1时, 可接受的回收率为50%~120%, 兽药残留水平1~10 μg·kg-1的回收率应为60%~120%, 10~1 000 μg·kg-1的回收率应为70%~120%。结果表明, 在三个加样水平下各化合物的回收率范围为70.4%~118.7%, 回收率均良好(表 4)。
在三个加样水平下, 一式六份重复性RSD为0.69%~12.07%, 重复性良好(表 4)。
53种化合物的稳定性RSD为2.16%~13.22%, 结果表明24 h内稳定性良好。
采用所建立的方法对27批山羊角样品进行了测定, 其中产地为内蒙古的2批样品分别检出艾司唑仑0.92 μg·kg-1和氧氟沙星10.78 μg·kg-1, 产地为浙江的2批样品分别检出氧氟沙星7.04、4.73 μg·kg-1。禁用兽药检出率为14.8%。
在我国, 艾司唑仑被禁止用于饲料和动物饮用水中; 氧氟沙星已停止用于食用动物, 其最大残留限量在GB31650.1-2022中规定为2 μg·kg-1。但在药用动物中是否禁用尚无明确规定。
山羊角主要由蛋白质类、多肽类、核苷类和无机元素类组成, 几乎不含脂肪。文献[33]报道, 纯乙腈作提取溶剂时添加一定的水相, 可以提高萃取效率, 并更有效地去除蛋白质或其他基质组分, 本方法采用乙腈水溶液作为提取溶剂。经实验比较, 于乙腈水溶液中加入无机盐可使两相分离, 去除水溶性基质成分干扰, 因此采用盐析辅助液液萃取作为提取方法。
研究中考察了3种提取溶剂[乙酸乙酯、乙腈、乙腈-乙酸乙酯(1∶1)], 结果表明乙酸乙酯对于氟喹诺酮类提取效率较差; 比较了提取溶剂的pH对提取效率的影响, 结果表明在1%甲酸乙腈溶液条件下提取效率最好。在盐析步骤中, 考察了NaCl-Na2SO4(1∶4)、NaCl-MgSO4(1∶4)、MgSO4-NaOAc(4∶1)、NaCl-MgSO4-柠檬酸三钠-柠檬酸氢二钠(1∶4∶1∶0.5) 四种盐包对回收率的影响, 结果表明NaCl-Na2SO4的回收率最好, 而加入MgSO4后释放大量的热导致部分化合物损失。
在评估净化方法时, 比较了5种方法: MCX、MAX、d-SPE、HLB和不净化。结果表明, MCX和MAX专属性较强, 不适用于多残留同时筛查; d-SPE和HLB会造成部分化合物的损失; 而提取后不净化的回收率普遍较好。
沙丁胺醇和莱克多巴胺等β2-受体激动剂类易在动物体内代谢发生醛酸化和硫酸化, 以游离态和结合态两种形式存在[34]。文献多采用酶解方式处理, 也有采用酸性条件下直接提取的报道[35]。本研究基于禁用兽药筛查的测定目的, 兼顾多数兽药的前处理, 采用酸性提取的方式主要针对游离态进行测定。如筛查为阳性结果, 可另行建立酶解方法准确测定。
由于外标法在定量某些化合物时准确性较差, 因此有必要采用内标法定量。内标的理化性质应与被定量化合物的性质相似, 因此使用稳定的同位素标记物作为内标是最佳选择。由于结构相似的化合物通常表现出相近的理化性质, 某一化合物的同位素内标可作为具有相似结构化合物的共用内标, 从而有助于降低检测成本。例如, β-受体激动剂的基本结构是β-苯乙醇胺, 西布特罗的[M+H]+母离子容易失去一个H2O和一个C4H8分子, 形成m/z 160的碎片离子。而大多数β-受体激动剂具相似的质谱裂解规律, 因此西布特罗-d9可用于西马特罗、特布他林、克仑特罗、西布特罗、溴布特罗和福莫特罗的定量。然而, 由于共馏出组分引起的基质效应, 具有相似保留时间的齐帕特罗和沙丁胺醇选择齐帕特罗-d7作为作内标。同样, 选择培氟沙星-d5、羟基甲硝唑-d2和2-QCA-d4分别作为氟喹诺酮类、硝基咪唑类和喹噁啉类的共用内标。
综上, 本研究建立的盐析辅助液液萃取结合UHPLC/MS/MS方法, 可用于定性定量检测山羊角中53种禁用兽药残留, 方法专属准确, 前处理简便, 已应用于实际样品的检测, 有效弥补了动物源性中药中兽药残留检测的空白, 发现了一定的安全风险。
作者贡献: 劳柏豪负责整体实验数据处理并撰写论文; 孙健负责指导实验方案设计并修改论文; 劳柏豪、张静娴、于泓、冉莹瑛、黄帆负责参与前处理实验; 季申、胡青对课题进行指导。
利益冲突: 本文无任何利益冲突。
  • 上海市科委研发平台专项(21DZ2290200)
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2025年第60卷第3期
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doi: 10.16438/j.0513-4870.2024-0995
  • 接收时间:2024-10-15
  • 首发时间:2025-11-06
  • 出版时间:2025-03-12
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  • 收稿日期:2024-10-15
  • 修回日期:2024-12-15
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上海市科委研发平台专项(21DZ2290200)
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    1.上海中医药大学中药学院, 上海 201203
    2.上海市食品药品检验研究院, 国家药品监督管理局中药质量控制重点实验室, 上海 201203

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*孙健, Tel: 18001678040, E-mail:
胡青, Tel: 18001677896, E-mail:
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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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