鸡组织中氯霉素残留检测方法及消除规律的研究
|
摘要
异氯霉素(meta-nitrochloramphenicol,m-CAP)是气相色谱(GC)检测氯霉素残留的一种内标物，用它作内标物是氯霉素痕量分析中提高定量准确性的一种有效方法，本文成功合成了氯霉素的同分异构体—异氯霉素，用它来作为氯霉素的气相色谱定量与气相色谱／质谱(GC／MS)联用确证检测方法的内标物。
本文成功建立了鸡肌肉和肝脏组织中氯霉素的气相色谱定量与气相色谱／质谱联用确证检测方法。乙酸乙酯提取，正己烷脱脂后，乙酸乙酯液液分配，加入异氯霉素(m-CAP)标准溶液作为内标物，蒸干，Sylon BFT衍生化后加入甲苯、蒸馏水处理，吸取上层有机相，取3μl进GC分析，1μl进GC／MS分析。气相色谱微电子捕获检测器(μECD)定量，鸡肌肉在0.1μg·kg~(-1)、1μg·kg~(-1)、20μg·kg~(-1)三个添加水平，平均回收率范围在82.8％～94.4％之间，日内变异系数范围在2.0％～4.5％(n=5)之间，日间变异系数范围在2.1％～12.7％(n=3)之间，检测限0.04 μg·kg~(-1)。鸡肝脏在0.2μg·kg~(-1)、1μg·kg~(-1)、20μg·kg~(-1)三个添加水平，平均回收率范围在69.1％～83.5％之间，日内变异系数范围在3.2％～8.2％(n=5)之间，日间变异系数范围在2.7％～8.0％(n=3)之间，检测限0.12 μg·kg~(-1)。质谱定性，质谱系统选择负离子化学电离(NICIMS)模式，选择离子m／z468，466，360，358，322和304检测。并在0.1μg·kg~(-1)(肝脏0.2μg·kg~(-1))、1μg·kg~(-1)、5μg·kg~(-1)三个添加水平对肌肉和肝脏成功进行了确证。
80只肉鸡分成3组，高剂量组(800 mg·kg~(-1)饲料)、低剂量组(200 mg·kg~(-1)饲料)和空白组，高、低剂量组连续饲喂添加氯霉素的饲料5天。试验结果表明，对照组中未检测出氯霉素残留。低剂量组，停药0h时，肌肉组织氯霉素平均残留水平为10.7μg·kg~(-1)；肝脏组织中氯霉素平均残留水平为0.73μg·kg~(-1)，停药12h时，肌肉中氯霉素平均残留水平为2.65μg·kg~(-1)，肝脏组织中未检出氯霉素残留，肌肉组织在停药8d时，未检测出氯霉素残留。高剂量组，停药0h时，肌肉组织氯霉素平均残留水平为42.1μg·kg~(-1)，肝脏组织中氯霉素平均残留水平为7.22μg·kg~(-1)，停药14d时，肌肉组织中未检测出氯霉素残留，而在停药24h时，肝脏组织已检测不到氯霉素残留。
Meta-nitrochloramphenicol (m-CAP) is a kind of internal standards used in gas chromatography for chloramphenicol (CAP) residue detection. It is an effective method for increasing accuracy of quantitativeness in trace analysis by using m-CAP as an internal standard in Chloramphenicol residue analysis. m-CAP was prepared successfully in this study.
In this paper a method was developed for determination of Chloramphenicol by gas chromatography and confirmation of Chloramphenicol by gas chromatography/mass spectrometry in broiler chicken muscles and livers.The tissues was extracted with ethyl acetate .The sample was defatted with hexane and extracted with ethyl acetate, then m-CAP was added to the sample, evaporated to dryness with nitrogen gas.Residue must be dry before adding Sylon N,O-Bis(trimethylsily) trifluoroacetamide (BFT).Added Sylon BFT.After derivatization, tolune and water were added directly to the sample .The organic layer was carefully removed.3ul analytes were determined by GC with micro electron capture detector(uECD) and 1ul confirmed by gas chromatography/ mass spectrometry. Analyzed by negative ion chemical ionization (NICIMS) with selected ion monitored.The ions with m/z 468,466,360,358,322,and 304 were monitor.The recoveries of analytes at the fortified level of 0.1ug. kg -1,1ug. kg-1,20 ug. kg-1 range from 82.8%~94.4% in the muscle , and at the fortified level of 0.2ug. kg-1, 1ug. kg-1,20 ug. kg-1 range from 69.1%-83.5% in the liver,respectively.Coefficents of variation for distribution,CVd,ranged from 2.0% to 4.5% in muscle, from 3.2% to 8.2% in liver,respectively.And for precision CVr,ranged from 2.1% to 12.7% in muscle,from 2.7% to 8.0% in liver,respectively.The limit of detection(LOD) is 0.04 ug. kg-1 in muscle, 0.12 u g. kg-1 in liver.
In feeding trial,eighty chicken was divided into 3 groups,high dosage group(800 mg. kg-1 feed),low dosage group(200 mg. kg-1 feed) and blank group,medicated 5 days continually.After the drug withdrawal, the concentrations of the Chloramphenicol residue in muscle and in liver were detected by GC.Fortified low dosage group,the Chloramphenicol residues were 10. 7ug. kg-1 and 2. 65ug. kg-1 at 0,12 hours.at the 8 days,below the LOD in muscle, the Chloramphenicol residues were 0. 73ug. kg-1 at 0 hours, at 12 hours, below the LOD in liver.Fortified high dosage group.the Chloramphenicol residues were 42. lug. kg-1, at the 14 days,below the LOD in muscle. The Chloramphenicol residues were 7. 22ug. kg-1 at 0 hours, at 24 hours, below the LOD in liver.
本文成功建立了鸡肌肉和肝脏组织中氯霉素的气相色谱定量与气相色谱／质谱联用确证检测方法。乙酸乙酯提取，正己烷脱脂后，乙酸乙酯液液分配，加入异氯霉素(m-CAP)标准溶液作为内标物，蒸干，Sylon BFT衍生化后加入甲苯、蒸馏水处理，吸取上层有机相，取3μl进GC分析，1μl进GC／MS分析。气相色谱微电子捕获检测器(μECD)定量，鸡肌肉在0.1μg·kg~(-1)、1μg·kg~(-1)、20μg·kg~(-1)三个添加水平，平均回收率范围在82.8％～94.4％之间，日内变异系数范围在2.0％～4.5％(n=5)之间，日间变异系数范围在2.1％～12.7％(n=3)之间，检测限0.04 μg·kg~(-1)。鸡肝脏在0.2μg·kg~(-1)、1μg·kg~(-1)、20μg·kg~(-1)三个添加水平，平均回收率范围在69.1％～83.5％之间，日内变异系数范围在3.2％～8.2％(n=5)之间，日间变异系数范围在2.7％～8.0％(n=3)之间，检测限0.12 μg·kg~(-1)。质谱定性，质谱系统选择负离子化学电离(NICIMS)模式，选择离子m／z468，466，360，358，322和304检测。并在0.1μg·kg~(-1)(肝脏0.2μg·kg~(-1))、1μg·kg~(-1)、5μg·kg~(-1)三个添加水平对肌肉和肝脏成功进行了确证。
80只肉鸡分成3组，高剂量组(800 mg·kg~(-1)饲料)、低剂量组(200 mg·kg~(-1)饲料)和空白组，高、低剂量组连续饲喂添加氯霉素的饲料5天。试验结果表明，对照组中未检测出氯霉素残留。低剂量组，停药0h时，肌肉组织氯霉素平均残留水平为10.7μg·kg~(-1)；肝脏组织中氯霉素平均残留水平为0.73μg·kg~(-1)，停药12h时，肌肉中氯霉素平均残留水平为2.65μg·kg~(-1)，肝脏组织中未检出氯霉素残留，肌肉组织在停药8d时，未检测出氯霉素残留。高剂量组，停药0h时，肌肉组织氯霉素平均残留水平为42.1μg·kg~(-1)，肝脏组织中氯霉素平均残留水平为7.22μg·kg~(-1)，停药14d时，肌肉组织中未检测出氯霉素残留，而在停药24h时，肝脏组织已检测不到氯霉素残留。
Meta-nitrochloramphenicol (m-CAP) is a kind of internal standards used in gas chromatography for chloramphenicol (CAP) residue detection. It is an effective method for increasing accuracy of quantitativeness in trace analysis by using m-CAP as an internal standard in Chloramphenicol residue analysis. m-CAP was prepared successfully in this study.
In this paper a method was developed for determination of Chloramphenicol by gas chromatography and confirmation of Chloramphenicol by gas chromatography/mass spectrometry in broiler chicken muscles and livers.The tissues was extracted with ethyl acetate .The sample was defatted with hexane and extracted with ethyl acetate, then m-CAP was added to the sample, evaporated to dryness with nitrogen gas.Residue must be dry before adding Sylon N,O-Bis(trimethylsily) trifluoroacetamide (BFT).Added Sylon BFT.After derivatization, tolune and water were added directly to the sample .The organic layer was carefully removed.3ul analytes were determined by GC with micro electron capture detector(uECD) and 1ul confirmed by gas chromatography/ mass spectrometry. Analyzed by negative ion chemical ionization (NICIMS) with selected ion monitored.The ions with m/z 468,466,360,358,322,and 304 were monitor.The recoveries of analytes at the fortified level of 0.1ug. kg -1,1ug. kg-1,20 ug. kg-1 range from 82.8%~94.4% in the muscle , and at the fortified level of 0.2ug. kg-1, 1ug. kg-1,20 ug. kg-1 range from 69.1%-83.5% in the liver,respectively.Coefficents of variation for distribution,CVd,ranged from 2.0% to 4.5% in muscle, from 3.2% to 8.2% in liver,respectively.And for precision CVr,ranged from 2.1% to 12.7% in muscle,from 2.7% to 8.0% in liver,respectively.The limit of detection(LOD) is 0.04 ug. kg-1 in muscle, 0.12 u g. kg-1 in liver.
In feeding trial,eighty chicken was divided into 3 groups,high dosage group(800 mg. kg-1 feed),low dosage group(200 mg. kg-1 feed) and blank group,medicated 5 days continually.After the drug withdrawal, the concentrations of the Chloramphenicol residue in muscle and in liver were detected by GC.Fortified low dosage group,the Chloramphenicol residues were 10. 7ug. kg-1 and 2. 65ug. kg-1 at 0,12 hours.at the 8 days,below the LOD in muscle, the Chloramphenicol residues were 0. 73ug. kg-1 at 0 hours, at 12 hours, below the LOD in liver.Fortified high dosage group.the Chloramphenicol residues were 42. lug. kg-1, at the 14 days,below the LOD in muscle. The Chloramphenicol residues were 7. 22ug. kg-1 at 0 hours, at 24 hours, below the LOD in liver.
引文
1. Ehrlich,J.,Bartz,Q.R.,Smith,R.M.,&Joslyn,D.A.,Chloromycetin, a New Antibiotic from a soil Actinomycete.Science., 1947,106:417
2．沈建忠，谢联金．兽医药理学．北京：中国农业大学出版社，2000
3. Edward H.Allen,Review of Chromatographic Methods for Chloramphenicol Residues in Milk,Eggs, and Tissues from Food-Producing Animals.J.AOAC., 1985,68:5,990～999
4．朱蓓蕾．动物性食品药物残留．上海科学技术出版社，1994
5. Huber W G.Aminoglycosides,Macrolides,Lincosarides,Polymyxins,Chloramphenicol,and Other Drugs,In:Both N H,Mcdonald L E Ed.Veterinary Pharmacology and Therapeutics.Fifth Edition,Ames:The Iowa State University Press, 1982,822～828
6. Feder H M,Jrosier C, Maderazo E G.Chloramphenicol:A Review of its use in clinical practise.Rev Infec Dis,1981,3:797～801
7. Kucers H.Current Position of Chloramphenicol Chemothrrapy. J Antimicrob C hemother, 1980,6:110～116
8. Settepani J A.The hazard of Using Chloramphenicol in food animal. J Am Vet Med Assoc, 1984,184:93011～93017
9. Plak BCP, Wesseling H, Herxeimer A, et al.Blood dyscrasias attributed to Chloramphenicol.A Review of s76 published and unpublished cases. Acta Med Stand, 1972,192:409～413
10. Fraungelder F T, Jr Bagby GC, Kelly D.Fatal aplastic anemia following topical administration of ophthalmic Chlormphenicol.Am J Ophthalmol, 1982,93:356～362
11．李俊锁，邱月明，王超著．兽药残留分析．上海科学出版社，2002，2
12．农业部文件，农牧发1999第17号，关于发布动物性食品中兽药最高残留限量的通知，1999，9，14
13．农业部文件，食品动物禁用的兽药及其他化合物清单，2002，3，4
14. Amold,Somgyl A.Trace Analysis of Chloramphenicol in Eggs,Milk, and Meat:Comparison of Gas Chromatography and Radioimmunoassay.J.AOAC., 1985,68:5,984～990.
15. Campbell GS,Mageau RP, Schwab B,et al. Antimicrob. Agents Chemother, 1984,25: 205～211
16. G.A.H.EI-Baradei,A Sensitive Enzyme Linked Immunosorbent Assay for Detection of Chloramphenicol Residues in Milk and Some Affecting Factors,Alex.J.Agric., 1997,42:2, 35～41
17. Gwendolyn S.Campbell,Richard P.Mageau,Bernard Schwab,and Ralph W.Johnston.,Detection and Quantitation of Chloramphenicol by Competitive Enzyme-Linked Immunoassay, Antimicrob. Agents Chemother., 1985,25:2,205～211
18. Van de Water, C.&Haagsma, N,Van Kooten, P.J.S.&Van Eden, W., An Enzyme-Linked Immunosorbent Assay for the Determination of Chloramphenicol Using A Monoclonal Antibody, Application to Residues in Swine Muscle Tissue,Zeitschrift F(?)r LebensmittelUntersuchung Undforschung, 1987,185:202～207
19. Russel HA.Liquid Chromatographic Analysis of Chloramphenicol in Bovine Muscles,Chromatographia, 1978,11:341～343
20. Pascal Sanders ,Philippe Guillot,Michele Dagorn,and Jean Michel Delams, Liquid Chromatographic Determination of Chloramphenicol in Calf Tissues:Studies of Stabilities in Muscles, Kidney, and Liver, J.AOAC., 1991,74:483～486
21. A.Simonella, L.Torreti,and C.Filipponi. Chloramphenicol:Solid-Phase Extration and HPLC Determination in Chicken Muscle,Organs,and Biological Fluids.J of High Resolution chrom.,1989.555～557
22. Austin R.Long,Lily C.Hsieh,Aola C.Bello,Marsla S.Malbrough Charles R.Short,and steven A.Barker.Method for the Isolation and Liquid Chromatography Determination of Chloramphenicol in Milk.Amer. Chemical Society.,1991,38:427～429
23. T.Nagata and M.Saeki,Simultaneous Determination of Thiamphenicol, Florfenicol,and Chloramphenicol Residue in Muscles of Animal and Cultured Fish by LC., 1992,15:12,2045～2046
24. M.Ramos,Th.Reuvers,A.Araanda, and J.Gomez. Determination of Chloramphenicol in Chilcken Muscle by HPLC and UV-Diode ArrayDetermination., 1994,17:2,385～401
25. Renem M.L. Aerts, Henkj, kenkens, and Geziena A.Werdmuller. Liquid Chromatography Determination of Chloramphenicol Residue in Meat:Interlaboratory study, J.AOAC., 1989, 72:570～576
26. T.L.Li,Y.J.Chung-Wang,and Y.C.Shih.Determination and Confirmation of Chloramphenicol Residues in Swine Muscle and Liver.J.of Food Science,2001,67:21～28
27. Jacobson WC, Allen EH.,Wiseman HG.,Determination of Chloramphenicol in Liver, Kidney, Muscle, and Whole Blood ,Prensent at 88th.,Annual Meeting of AOAC., 1974,10:14～17
28. J.R.Nelson, K.F.T. Copeland, R.J.Forster, D.J.Campbell and W.D.Blaek.Sensitive Gas-Liquid Chromatographic Method for Chloramphenicol in Animal Tissues Using ECD.J.of Chroma.,1983, 276:438～444
29. Robert K.Munns,David C.Holland,jose E.Roybal,Joseph M.Storey, and AustinR.Long, GC Determination of Chloramphenicol Residues in Shrimp:Interlaboratory Study, 1994, 77:3,596～601
30. Allen P.Pfenning,Jose E.Roybal,Heidis Rupp,Sherri B.Turnipseed,Steve A.Gonzales,and Jeffrey A.Hurlbut, Simultaneous Determination of Residues of Chloramphenicol,Florfenicol,Florfenicol Amine,and Thiamphenicol in Shrimp Tissue by GC with ECD.,J.AOAC.2000,83:26～30
31. M.Humayoun Akhtar, Claude Davis,Anadre Sauve,Carla Barry.Gas Chromatographic Determination of Incurred Chloramphenicol Residue in Eggs Foiling Optiomal Extraction.J.of Chroma., 1995,696:123～130
32. Keukens HJ, Analytical Strategy for the Regulatory Control of Residues of CAP in Meat:Preliminary studies in Milk.J AOAC,1992,75:245～256
33. Pfenning AP, Mark R .Madson,Jos(?) E . Royal, et al.Simultaneous Determination of CAP, FF, TAP Residues in Milk by Gas Chromatography with ECD. J AOAC, 1998 81:714～720
34. Nelson ,J.R; Copeland, K.F.T.; Forster, R.J;Campbell,D. Simultaneous Determination of
Thiamphenicol,Florfenicol,and Chloramphenicol Residue in Muscles of Animal by GC.J.,chramatogr. 1983,276,438
35. M. Humayoun Akhtar, Chaude Danis Andre Sauve, Carla Barry. Gas chromatographic determination of incurred chloramphenicol residues in eggs following. Optimal extraction. J of chromatogr, 1995,696: 123～130
36. Arnold,D.,&Somogyi,A. Trace Analysis of CAP Residues in Eggs,Milk and Meat:Comparison of GC and Radioimmunoassay.J.Assoc.Off.Anal.Chem. 1985,68:984～990
37. Delepine B,Sanders P.Determination of Chloramphenicol in muscle using a partical beam interface for combining liquid chromatography with negative ionization mass spectrometry.J Chroma., 1992,582:113
38. Philp James Kijak.Confirmation of Chloramphenicol Residue in Bovine Milk by GC-MS.,J.AOAC. 1994,77:34～40
39. Victor Hormazabal and Magne Yndestand. Simultaneous Determination of Chloramphenicol and Ketoprofen in Meat and Milk and Chloramphenicol in Egg ,Honey ,and Urine Using LC-MS.J.LC.& Rel. Technol.,2001,24(16):2477～2486
40. L.A.Ginkel,H.J.Van. Rossum,P.W.Zoontjes,H.Van Blitlersuijk, G.Ellen,E.Van.Der.Heeft, A.P.J. M.De.Jong and G.Zomer, Development and Validation of a GC-MS Procedure for the Identification and Quantification of Residues of Chloramphenicol, Analytical Chimica Acta., 1990,237:61～69
41. Kathleen P.Holland,A.Carolyn Herry, Roger T.Wilson,and John S.Dreas.Four-laboratory Validation Study of the Determination of Chloramphenicol in Veal Calf Urine.J AOAC.,1995,78:2,483～491
42. Steffen Borner, Hildburg Fry, Gabor Balizs,and Reinhard Kroker, Confirmation of Chloramphenicol Resudues in Egg by GC-HRMS and Comparison of Quantitation with GC-ECD.J.AOAC., 1995,78(5): 1153～1160
43. Tomoko NagaTa and Hisao Oka, Determination of Residual Chloramphenicol ,Florfenicoll,and Thiamphenicol in Yellowtail Fish Muscles by Capillary GC-MS., 1996,44:1280～1284
44. Robert L.Epstein,International Validation Study for the Determination of Chloramphenicol in Bovine Muscle,J.AOAC., 1994,77(3):570～576
45. Richard K. Hill, Peter N. Nμ gara.Separation and Stereochemical Assignment of Erythro and Threo Isomers of the m-Nitro Analogue of (±)-Chloramphenicol J Org.chem.. 1992,1045～1047
46. Long L.M.,Troutman H.D.Chloramphenicol(Chloromycetin). Ⅶ.Synthesis through p-Nitroacetophenone.THIS JOURNAL. 1949,71:2473～2475
47. Kenkuns H J,Beek W M,Aerts M M L.High Performance Liquid Chromatography Screening and Confirmation Methods for CAP Residues in Meat with off-line Cartridge Sample Clean-up and on-line diode array UV-VIS detection. J Chroma.,1986,325:445～453
48. Bergner Lang,B.,&K(?)chele,M. Dtsch.Lebensm.Rundsch. 1985,81:278～284
49. Malisch,R. Z.Method for the simultaneous determination of residues of chemotherapeutic agents,antiparasitic agents and growth promoters in food of animal origin.Determination of chloramphenicol and meticlorpindol.Lebensm.Unters.Forsch. 1987,184:467～471
50. Amold,D.,&Somogyi,A. Trace Analysis of CAP Residues in Eggs,Milk and Meat:Comparison of GC and Radioimmunoassay.J.Assoc.Off.Anal.Chem. 1985,68:984～990
51. Furst,P.,Kruger,Chr.,Meemken,H.A.,&Groebel,W. Multivariate statistical approach to a date set of dioxin and furan contaminations in human milk.Dtsch.Lebensm.Rundsch. 1988,84:108
52. USDA FSIS(1991)Analytical Chemistry Laboratory Guidebook, Residue Chemistry Section,U.S.Govemment Prining Office, Washington, DC, pp.CAMU 1～30
53. Robert L.Epstein,International Validation Study for the Determination of Chloramphenicol in Bovine Muscle,J.AOAC., 1994,77:3, 576
2．沈建忠，谢联金．兽医药理学．北京：中国农业大学出版社，2000
3. Edward H.Allen,Review of Chromatographic Methods for Chloramphenicol Residues in Milk,Eggs, and Tissues from Food-Producing Animals.J.AOAC., 1985,68:5,990～999
4．朱蓓蕾．动物性食品药物残留．上海科学技术出版社，1994
5. Huber W G.Aminoglycosides,Macrolides,Lincosarides,Polymyxins,Chloramphenicol,and Other Drugs,In:Both N H,Mcdonald L E Ed.Veterinary Pharmacology and Therapeutics.Fifth Edition,Ames:The Iowa State University Press, 1982,822～828
6. Feder H M,Jrosier C, Maderazo E G.Chloramphenicol:A Review of its use in clinical practise.Rev Infec Dis,1981,3:797～801
7. Kucers H.Current Position of Chloramphenicol Chemothrrapy. J Antimicrob C hemother, 1980,6:110～116
8. Settepani J A.The hazard of Using Chloramphenicol in food animal. J Am Vet Med Assoc, 1984,184:93011～93017
9. Plak BCP, Wesseling H, Herxeimer A, et al.Blood dyscrasias attributed to Chloramphenicol.A Review of s76 published and unpublished cases. Acta Med Stand, 1972,192:409～413
10. Fraungelder F T, Jr Bagby GC, Kelly D.Fatal aplastic anemia following topical administration of ophthalmic Chlormphenicol.Am J Ophthalmol, 1982,93:356～362
11．李俊锁，邱月明，王超著．兽药残留分析．上海科学出版社，2002，2
12．农业部文件，农牧发1999第17号，关于发布动物性食品中兽药最高残留限量的通知，1999，9，14
13．农业部文件，食品动物禁用的兽药及其他化合物清单，2002，3，4
14. Amold,Somgyl A.Trace Analysis of Chloramphenicol in Eggs,Milk, and Meat:Comparison of Gas Chromatography and Radioimmunoassay.J.AOAC., 1985,68:5,984～990.
15. Campbell GS,Mageau RP, Schwab B,et al. Antimicrob. Agents Chemother, 1984,25: 205～211
16. G.A.H.EI-Baradei,A Sensitive Enzyme Linked Immunosorbent Assay for Detection of Chloramphenicol Residues in Milk and Some Affecting Factors,Alex.J.Agric., 1997,42:2, 35～41
17. Gwendolyn S.Campbell,Richard P.Mageau,Bernard Schwab,and Ralph W.Johnston.,Detection and Quantitation of Chloramphenicol by Competitive Enzyme-Linked Immunoassay, Antimicrob. Agents Chemother., 1985,25:2,205～211
18. Van de Water, C.&Haagsma, N,Van Kooten, P.J.S.&Van Eden, W., An Enzyme-Linked Immunosorbent Assay for the Determination of Chloramphenicol Using A Monoclonal Antibody, Application to Residues in Swine Muscle Tissue,Zeitschrift F(?)r LebensmittelUntersuchung Undforschung, 1987,185:202～207
19. Russel HA.Liquid Chromatographic Analysis of Chloramphenicol in Bovine Muscles,Chromatographia, 1978,11:341～343
20. Pascal Sanders ,Philippe Guillot,Michele Dagorn,and Jean Michel Delams, Liquid Chromatographic Determination of Chloramphenicol in Calf Tissues:Studies of Stabilities in Muscles, Kidney, and Liver, J.AOAC., 1991,74:483～486
21. A.Simonella, L.Torreti,and C.Filipponi. Chloramphenicol:Solid-Phase Extration and HPLC Determination in Chicken Muscle,Organs,and Biological Fluids.J of High Resolution chrom.,1989.555～557
22. Austin R.Long,Lily C.Hsieh,Aola C.Bello,Marsla S.Malbrough Charles R.Short,and steven A.Barker.Method for the Isolation and Liquid Chromatography Determination of Chloramphenicol in Milk.Amer. Chemical Society.,1991,38:427～429
23. T.Nagata and M.Saeki,Simultaneous Determination of Thiamphenicol, Florfenicol,and Chloramphenicol Residue in Muscles of Animal and Cultured Fish by LC., 1992,15:12,2045～2046
24. M.Ramos,Th.Reuvers,A.Araanda, and J.Gomez. Determination of Chloramphenicol in Chilcken Muscle by HPLC and UV-Diode ArrayDetermination., 1994,17:2,385～401
25. Renem M.L. Aerts, Henkj, kenkens, and Geziena A.Werdmuller. Liquid Chromatography Determination of Chloramphenicol Residue in Meat:Interlaboratory study, J.AOAC., 1989, 72:570～576
26. T.L.Li,Y.J.Chung-Wang,and Y.C.Shih.Determination and Confirmation of Chloramphenicol Residues in Swine Muscle and Liver.J.of Food Science,2001,67:21～28
27. Jacobson WC, Allen EH.,Wiseman HG.,Determination of Chloramphenicol in Liver, Kidney, Muscle, and Whole Blood ,Prensent at 88th.,Annual Meeting of AOAC., 1974,10:14～17
28. J.R.Nelson, K.F.T. Copeland, R.J.Forster, D.J.Campbell and W.D.Blaek.Sensitive Gas-Liquid Chromatographic Method for Chloramphenicol in Animal Tissues Using ECD.J.of Chroma.,1983, 276:438～444
29. Robert K.Munns,David C.Holland,jose E.Roybal,Joseph M.Storey, and AustinR.Long, GC Determination of Chloramphenicol Residues in Shrimp:Interlaboratory Study, 1994, 77:3,596～601
30. Allen P.Pfenning,Jose E.Roybal,Heidis Rupp,Sherri B.Turnipseed,Steve A.Gonzales,and Jeffrey A.Hurlbut, Simultaneous Determination of Residues of Chloramphenicol,Florfenicol,Florfenicol Amine,and Thiamphenicol in Shrimp Tissue by GC with ECD.,J.AOAC.2000,83:26～30
31. M.Humayoun Akhtar, Claude Davis,Anadre Sauve,Carla Barry.Gas Chromatographic Determination of Incurred Chloramphenicol Residue in Eggs Foiling Optiomal Extraction.J.of Chroma., 1995,696:123～130
32. Keukens HJ, Analytical Strategy for the Regulatory Control of Residues of CAP in Meat:Preliminary studies in Milk.J AOAC,1992,75:245～256
33. Pfenning AP, Mark R .Madson,Jos(?) E . Royal, et al.Simultaneous Determination of CAP, FF, TAP Residues in Milk by Gas Chromatography with ECD. J AOAC, 1998 81:714～720
34. Nelson ,J.R; Copeland, K.F.T.; Forster, R.J;Campbell,D. Simultaneous Determination of
Thiamphenicol,Florfenicol,and Chloramphenicol Residue in Muscles of Animal by GC.J.,chramatogr. 1983,276,438
35. M. Humayoun Akhtar, Chaude Danis Andre Sauve, Carla Barry. Gas chromatographic determination of incurred chloramphenicol residues in eggs following. Optimal extraction. J of chromatogr, 1995,696: 123～130
36. Arnold,D.,&Somogyi,A. Trace Analysis of CAP Residues in Eggs,Milk and Meat:Comparison of GC and Radioimmunoassay.J.Assoc.Off.Anal.Chem. 1985,68:984～990
37. Delepine B,Sanders P.Determination of Chloramphenicol in muscle using a partical beam interface for combining liquid chromatography with negative ionization mass spectrometry.J Chroma., 1992,582:113
38. Philp James Kijak.Confirmation of Chloramphenicol Residue in Bovine Milk by GC-MS.,J.AOAC. 1994,77:34～40
39. Victor Hormazabal and Magne Yndestand. Simultaneous Determination of Chloramphenicol and Ketoprofen in Meat and Milk and Chloramphenicol in Egg ,Honey ,and Urine Using LC-MS.J.LC.& Rel. Technol.,2001,24(16):2477～2486
40. L.A.Ginkel,H.J.Van. Rossum,P.W.Zoontjes,H.Van Blitlersuijk, G.Ellen,E.Van.Der.Heeft, A.P.J. M.De.Jong and G.Zomer, Development and Validation of a GC-MS Procedure for the Identification and Quantification of Residues of Chloramphenicol, Analytical Chimica Acta., 1990,237:61～69
41. Kathleen P.Holland,A.Carolyn Herry, Roger T.Wilson,and John S.Dreas.Four-laboratory Validation Study of the Determination of Chloramphenicol in Veal Calf Urine.J AOAC.,1995,78:2,483～491
42. Steffen Borner, Hildburg Fry, Gabor Balizs,and Reinhard Kroker, Confirmation of Chloramphenicol Resudues in Egg by GC-HRMS and Comparison of Quantitation with GC-ECD.J.AOAC., 1995,78(5): 1153～1160
43. Tomoko NagaTa and Hisao Oka, Determination of Residual Chloramphenicol ,Florfenicoll,and Thiamphenicol in Yellowtail Fish Muscles by Capillary GC-MS., 1996,44:1280～1284
44. Robert L.Epstein,International Validation Study for the Determination of Chloramphenicol in Bovine Muscle,J.AOAC., 1994,77(3):570～576
45. Richard K. Hill, Peter N. Nμ gara.Separation and Stereochemical Assignment of Erythro and Threo Isomers of the m-Nitro Analogue of (±)-Chloramphenicol J Org.chem.. 1992,1045～1047
46. Long L.M.,Troutman H.D.Chloramphenicol(Chloromycetin). Ⅶ.Synthesis through p-Nitroacetophenone.THIS JOURNAL. 1949,71:2473～2475
47. Kenkuns H J,Beek W M,Aerts M M L.High Performance Liquid Chromatography Screening and Confirmation Methods for CAP Residues in Meat with off-line Cartridge Sample Clean-up and on-line diode array UV-VIS detection. J Chroma.,1986,325:445～453
48. Bergner Lang,B.,&K(?)chele,M. Dtsch.Lebensm.Rundsch. 1985,81:278～284
49. Malisch,R. Z.Method for the simultaneous determination of residues of chemotherapeutic agents,antiparasitic agents and growth promoters in food of animal origin.Determination of chloramphenicol and meticlorpindol.Lebensm.Unters.Forsch. 1987,184:467～471
50. Amold,D.,&Somogyi,A. Trace Analysis of CAP Residues in Eggs,Milk and Meat:Comparison of GC and Radioimmunoassay.J.Assoc.Off.Anal.Chem. 1985,68:984～990
51. Furst,P.,Kruger,Chr.,Meemken,H.A.,&Groebel,W. Multivariate statistical approach to a date set of dioxin and furan contaminations in human milk.Dtsch.Lebensm.Rundsch. 1988,84:108
52. USDA FSIS(1991)Analytical Chemistry Laboratory Guidebook, Residue Chemistry Section,U.S.Govemment Prining Office, Washington, DC, pp.CAMU 1～30
53. Robert L.Epstein,International Validation Study for the Determination of Chloramphenicol in Bovine Muscle,J.AOAC., 1994,77:3, 576