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Home , Bolasterone, Clostebol, Clostebol acetate, Cyclofenil, Delmadinone acetate, Formebolone

University of Groningen

Multi-residue analysis of growth promotors in food-producing animals Koole, Anneke

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Publication date: 1998

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA): Koole, A. (1998). Multi-residue analysis of growth promotors in food-producing animals. s.n.

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Download date: 25-09-2021 APPENDIX 1 OVERVIEW OF RELEVANT SUBSTANCES

This appendix consists of two parts. First, substances that are relevant for the research presented in this thesis are given. For each substance CAS number (CAS), molecular weight (MW), bruto formula (formula) and if available UV maxima and alternative names are given. In addition, pKa values for the ß- are listed, if they were available. Not all ß-agonists have a CAS number. For the relevant anabolic and related substances, maximum residue limits (MRLs) and safe concentrations (safe conc) as defined by the FDA have been included. In the second part of this appendix, the structural formulas of the substances used in the experiments are given. Abbreviations used: ac under acidic conditions, alk under alkaline conditions, MeOH methanol, EtOH ethanol, m muscle, f fat, k kidney, l liver.

217 Appendix 1

ß-Agonists substance CAS MW formula

bamethane 3703-79-5 209.29 C12H19NO2 brombuterol 41937-02-4 365.00 C12H18N2OBr2 broom-clenbuterol 321.64 C12H18N2OClBr broom-clenproperol 352.07 C11H16N2OBr2 broom-mapenterol 369.22 C14H20N2OF3Br carbuterol 34866-47-2 267.33 C13H21N3O3 cimaterol 54239-37-1 219.29 C12H17N3O cimbuterol 54239-39-3 233.31 C13H19N3O clenbuterol 37148-27-9 277.19 C12H18N2OCl2 clencyclohexerol 319.23 C14H20N2O2Cl2 clenhepterol 319.27 C15H24N2OCl2 clenhexerol 305.25 C14H22N2OCl2 clenisopenterol 291.22 C13H20N2OCl2 clenpenterol 291.22 C13H20N2OCl2 clenproperol 263.17 C11H16N2OCl2 fenoterol 13392-18-2 303.37 C17H21NO4 hydroxy-clenbuterol 293.19 C12H18N2O2Cl2 hydroxy-clenhepterol 335.27 C15H24N2O2Cl2 isoprenaline 7683-59-2 211.26 C11H17NO3 N-isopropyl-clenbuterol 319.27 C15H24N2OCl2 L-644,969 103583-08-0 285.39 C17H23N3O mabuterol 56341-08-3 310.75 C13H18N2OClF3 mahexerol 338.80 C15H22N2OClF3 mapenterol 95656-68-1 324.75 C14H20N2OClF3 metaproterenol 586-06-1 211.26 C11H17NO3 3-methyl-mapenterol 338.80 C15H22N2OClF3 N-methyl-mapenterol 338.80 C15H22N2OClF3 pirbuterol 38677-81-5 240.30 C12H20N2O3 ractopamine 97825-25-7 301.39 C18H23NO3 salbutamol 18559-94-9 239.31 C13H21NO3 terbutaline 23031-25-6 225.29 C12H19NO3 tulobuterol 41570-61-0 227.73 C12H18NOCl

218 Overview of Relevant Substances

pKa UV alternative names Ac alk unknown 9 10.2 275 242, 290 brenbuterol

249, 325

< 1 9.6 245, 300

iso-propylclenproperol 8.5 10 275 295 231, 280

8.6 10.1 12 279 297 231, 280 isoproterenol

245, 300

9 10.1 11.4 276 297 orciprenaline

231, 280 9.3 10.3 276 245 231, 280 albuterol 8.7 10 11 276 297 231, 280

219 Appendix 1

Anabolic steroids and related substances Substance CAS MW formula

acetophenide 24356-94-3 448.60 C29H36O3 432-60-0 300.47 C21H32O Allyltrenbolone 850-52-2 310.44 C21H26O2 521-18-6 290.40 C19H30O2 19793-20-5 276.42 C18H28O2 1605-89-6 316.47 C21H32O2 846-48-0 286.41 C19H26O2 broparoestrole 479-68-5 363.31 C22H19Br 17021-26-0 316.49 C21H32O2 1961-77-9 362.90 C21H27O3Cl chlormadinone 302-22-7 404.90 C23H29O3Cl 1093-58-9 322.89 C19H27O2Cl cyclofenil 2624-43-3 364.44 C23H24O4 cyproteron 2098-66-0 374.92 C22H27O3Cl 17230-88-5 337.47 C22H27NO2 dehydrochloromethyl 2446-23-3 334.89 C20H27O2Cl acetate 13698-49-2 402.92 C23H27O4Cl 84-17-3 266.32 C18H18O2 56-53-1 268.34 C18H20O2 79-64-1 340.51 C23H32O2 58-19-5 304.47 C20H32O2 152-62-5 312.50 C21H28O2 epi-nortestosterone 4409-34-1 274.40 C18H26O2 epi-testosterone 481-30-1 288.43 C19H28O2 epi- 80657-17-6 270.37 C18H22O2 7004-98-0 302.42 C19H26O3 434-03-7 312.45 C21H28O2 965-90-2 288.46 C20H32O ethynodiol 1231-93-2 300.42 C20H28O2 ethynyloestradiol 57-63-6 296.41 C20H24O2 76-43-7 336.45 C20H29O3F 2454-11-7 344.45 C21H28O4 gestonorone-caproate 1253-28-7 414.59 C26H38O4 84-16-2 270.36 C18H22O2 17 -hydroxy- 68-96-2 330.50 C21H30O3 lynestrol 52-76-6 284.44 C20H28O 977-79-7 340.51 C23H32O2 520-85-4 344.49 C22H32O3 medroxyprogesterone acetate 71-58-9 386.53 C24H34O4

220 Overview of Relevant Substances

UV alternative names/information no absorption (230-360 nm)

stanolone

285 MeOH

247 (ac), 262 (alk) EtOH induction of

241 EtOH 240 EtOH drostalone 286 EtOH metabolite metabolite metabolite

240 EtOH no absorption (230-360 nm)

281 EtOH 240 EtOH formyldienolone 240 MeOH hexanoate 230, 280 EtOH; 242, 297 (alk) 240 EtOH no absorption (230-360 nm) ethynylestrenol

241 EtOH

221 Appendix 1

substance CAS MW formula

acetate 595-33-5 384.52 C23H32O4 5633-18-1 354.47 C23H30O3 2919-66-6 396.53 C25H32O4 521-11-9 304.46 C20H32O2 434-05-9 304.47 C20H32O2 72-33-3 310.44 C31H26O2 72-63-9 300.44 C20H28O2 153-00-4 302.44 C20H30O2 521-10-8 304.46 C20H32O2 methylestrenolone 514-61-4 288.43 C19H28O2 58-18-4 302.46 C20H30O2 methyltrienolone 965-93-5 284.38 C19H24O2 3704-09-4 302.46 C20H30O2 434-22-0 274.40 C18H26O2 52-78-8 302.46 C20H30O2 68-22-4 298.43 C20H26O2 norethynodrel 68-23-5 298.43 C20H26O2 dl- 6533-00-2 312.45 C21H28O2 norprogesterone 472-54-8 300.46 C20H28O2 6795-60-4 300.42 C20H28O2 17 -oestradiol 57-91-0 272.39 C18H24O2 17ß-oestradiol 50-28-2 272.39 C18H23O2 oestriol 50-27-1 288.39 C18H24O3 oestrone 53-16-7 270.37 C18H22O2 53-39-4 306.45 C19H30O3 145-12-0 318.44 C20H30O3 434-07-1 332.48 C21H32O3 progesterone 57-83-0 314.47 C21H30O2 2487-63-0 352.52 C24H33O2 152-43-2 364.51 C25H32O2 10418-03-8 328.48 C21H32N2O 5197-58-0 302.44 C20H30O2 42422-68-4 322.41 C18H26O5 10540-29-1 371.53 C26H29NO testosterone 58-22-0 288.43 C19H28O2 trenbolone 10161-33-8 270.37 C18H22O2 vinyltestosterone 314.47 C21H30O2 17924-92-4 318.36 C18H22O5 55331-29-8 322.41 C18H26O5

222 Overview of Relevant Substances

UV alternative names/information 287 EtOH

MRL (ppb) 25 (f, melengestrol acetate) no absorption (230-360 nm) 278, 287 MeOH methandrostenolone, dianabol, methylboldenone methenolone

241 EtOH

240 EtOH nortestosterone 240 EtOH 240 EtOH norethindrone no absorption (230-360 nm)

metabolite 231 EtOH MRL (ppt) 120 (m), 480 (f), 360 (k), 240 (l) 280 EtOH 280 EtOH

277 (ac), 315 (alk) MeOH 240 EtOH MRL (ppb) 3 (m), 12 (f), 9 (k), 6 (l)

230 (ac) MeOH

240 EtOH MRL (ppb) 0.64 (m), 2.6 (f), 1.9 (k), 1.3 (l) safe conc (ppb) 50 (m), 100 (l), 150 (k), 200 (f)

236, 274, 316 MeOH mycotoxin 218, 265, 304 MeOH safe conc (ppb) 150 (m), 300 (l), 450 (k), 600 (f)

223 Appendix 1

ANDROGENS

OH OH CH3 CH 3 CH3

CH3

O O

nortestosterone methyltestosterone

OH OH CH3 CH3 CH3

CH3 CH3

N O N testosterone H stanozolol

OH OH CH3 CH3

CH3 CH3

O OH Cl Cl clostebol clostebol-diol

OH CH3

O trenbolone

224 Overview of Relevant Substances

OESTROGENS OH O CH3 CH3

OH OH oestradiol oestrone

OH OH CH3 CH3 CH OH C

OH OH

oestriol ethynyl oestradiol

PROGESTAGENS

CH3 CH3 C O CH C O 3 CH 3 CH3

CH3 CH3

O O progesterone CH3 medrogestone

CH3 C O CH3 OH

CH3

O

CH3 medroxyprogesterone

225 Appendix 1

RESORCYLIC ACID LACTONES

OH O CH3 OH O CH3

O O

OH OH

O OH zearalenone zeranol

OH O CH3

O

OH

OH

taleranol

STILBENES

CH3 C2H5 C OH C OH C C OH C OH C2H5 C CH3

diethylstilbestrol dienoestrol

C2H5 OH C H H C OH

C2H5

hexoestrol

226 Overview of Relevant Substances

BETA-AGONISTS

CN Cl OH H CH3 OH H CH3

NH2 C C N C H NH2 C C N C CH3

H H H CH3 H H H CH3 Cl cimaterol clenbuterol

OH CF3 OH H CH3 OH H CH3

C C N C H NH2 C C N C CH3

H H H CH2 OH H H H CH3 OH Cl

fenoterol mabuterol

CH2OH OH OH H CH3 OH H CH3

OH C C N C CH3 C C N C CH3 H H H CH H H H CH3 3 OH

salbutamol terbutaline

Br CF3 OH H CH3 OH H CH3

NH2 C C N C CH3 NH2 C C N C CH3

H H H CH3 H H H C2H5 Br Cl

brombuterol mapenterol

227 APPENDIX 2 GLOSSARY OF TERMINOLOGY FOR BOVINE ANIMALS

Bull: mature, non-castrated male bovine, usually used for breeding Calf: young bovine, either male or female; usually under 1 year of age Castrate: remove testicle from male animal, geld Cow: mature female bovine that has given birth and is lactating Cull cow: animal too old for breeding, being fattened before slaughter Heifer: female bovine old enough to breed but which has not yet calved; also used for young cow that only recently had her first calf Ox: castrated male bovine used as draught animal or reared for food; also used for any bovine animal Ruminant: cud-chewing animal with four-component stomach Steer: male bovine castrated at young age; in US castrated male of any age Vasectomised animal: male animal that has been rendered sterile by removal of portion of vas deferens; it will still exhibit libido Veal: young dairy calf, under 12 weeks of age, kept in the dark and fed only milk or milk replacer; used to produce pale, soft and tender carcass; also used to identify particular food product Yearling: animal of approximately 1 year of age

This glossary was compiled from: · Cattle Industry, in: D.F. McBride, Learning Veterinary Terminology, Mosby, St Louis MI, ISBN 0-8151-5960-9, 1996, p 453-479 · Growth Promoters and , in: N.T. Crosby, Determination of Veterinary Residues in Food, Ellis Horwood Series in Food Science and Technology, Ellis Horwood, Chisester, 1991, ISBN 0-7476-0065-1, Chapter 6, p 148-176 · J. Coulson, L. Hutchinson, C.T. Carr, D. Eagle, H.M. Petter and J. Hawkins (ed), The Oxford Illustrated Dictionary, Book Club Associates, London, second edition, 1980

229 APPENDIX 3 ABBREVIATIONS

: selectivity factor in chromatography AD: ADS: alkyl-diol silica AIR: agro-industrial research program of the European Union ANOVA: analysis of variance APCI: atmospheric pressure chemical ionisation avg: average C2: ethyl bonded silica C8: octyl bonded silica C18: octadecyl bonded silica CC: colour code(s) CER: Laboratoire d’Hormonologie, Centre d’Economie Rurale, Marloie, cDES: cis-diethylstilbestrol Clen: clenbuterol hydrochloride ClTac: , 4-chlorotestosterone acetate ClTdiol: clostebol-diol conc: concentration CRL: Community Reference Laboratory CV: coefficient of variation DE: dienoestrol DES: diethylstilbestrol du: digital units, used in IMS E1: oestrone E2: 17ß-oestradiol E2benz: 17ß-oestradiol benzoate ECD: electrochemical detection EE2: 17 -ethynyl oestradiol EU: European Union FDA: Food and Administration (USA) Feno: fenoterol hydrobromide

231 Appendix 3

GC: gas chromatography HEX: hexoestrol HPLC: high performance liquid chromatography hRf: retention parameter used in TLC IAC: immuno-affinity chromatography IMS: mobility spectrometry, ion mobility spectrometer k’: capacity factor in chromatography

K0: reduced mobility in IMS LC: liquid chromatography LLE: liquid-liquid extraction LOD: limit of detection, detection limit LRMS: low resolution mass spectrometry MED: medrogestone mIAC: multi immuno-affinity chromatography MP: medroxyprogesterone MRL: maximum residue limit MS: mass spectrometry MSD: mass selective detection, mass selective detector MSPD: matrix solid phase dispersion MT: methyltestosterone MTSS: Merck Tox Screening System MW: molecular weight N: theoretical plate number NRL: National Reference Laboratory NT: 19-17 -nortestosterone ßNT: 19-17ß-nortestosterone NTA: P: progesterone PBS: phosphate buffered saline PFTE: polytetrafluoroethylene, teflon RI: retention index RIA: radio immunoassay RIVM: Laboratory for Residue Analysis/Community Reference Laboratory, RIVM, Bilthoven, The Rs: resolution in chromatography RT: retention time

232 Abbreviations

RTc: corrected retention time Sal: salbutamol sulphate SCX: strong cation exchanger sd: standard deviation SDB: poly(styrenedivinylbenzene) SEM: standard error SI: similarity index SPE: solid phase extraction STA: systematic toxicological analysis Stan: stanozolol T: testosterone Tal: taleranol Tb: ß-trenbolone TBME: t-butyl methyl ether tDES: trans-diethylstilbestrol Terb: terbutaline sulphate TLC: thin-layer chromatography w0.5: peak width at half maximum WTO: World Trade Organisation Zeara: zearalenone Zer: zeranol

233