doi: 10.14202/vetworld.2018.731-738
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Article history: Received: 10-01-2018, Accepted: 24-04-2018, Published online: 01-06-2018
Corresponding author: Lazuardi Mochamad
E-mail: lazuardi@fkh.unair.ac.id
Citation: Mochamad L, Hermanto B, Restiadi TI (2018) Calculate of withdrawal times of clenbuterol in goats to obtain safe times of slaughter, Veterinary World, 11(6): 731-738.Background and Aim: Clenbuterol as a β2-agonist drug was investigated according to the concentration of the drug available in the bodies of goats and according to the level of sensitivity of the instruments used for detection. The objective of the current study was to determine withdrawal times after giving a therapeutic dose that resulted in safe slaughters.
Materials and Methods: Five healthy male goats with a mean body weight of 20.64 kg were treated with a single dose of 5.10-3 mg/kg in the BW onto jugular vein. Whole blood samples of approximately 5 mL were taken in a time series at 5, 30, 60, 90, 150, 210, 270, 390, 510, 630, and 750 min. At 24 h posttreatment, all subjects were sacrificed, and 300 g samples of the liver were obtained. The plasma concentration and liver residue of the drug were observed by reverse-phase high-performance liquid chromatography.
Results: The drug reached a maximum concentration of 19.233±0.331 μg/mL at 5 min, and the elimination half-life was at 173.25 min. The limit detection was obtained at 0.053 μg/mL. A one-way analysis of variance between all goats showed that elimination of the clenbuterol in their bodies was similar (p=1.00), with a withdrawal time of 1,479.326 min and no residues in the liver (p<0.05).
Conclusion: Safe times for slaughter were determined to be at 2 days, 13 h, and 12 min as the 2nd safety factor (SF) time and 3 days, 1 h, and 58 min as the 3rd SF time with the liver organ free from residue.
Keywords: elimination half-life, new method for calculating withdrawal time, prescriptions for obtained β2-agonist, residues in liver.
1. Grimmer, N.M., Gimbar, R.P., Bursua, A. and Patel, M. (2016) Rhabdomyolysis secondary to clenbuterol use and exercise. J. Emerg. Med., 50: e71-e74. [Crossref]
2. Liu, X., Grandy, D.K. and Janowsky, A. (2014) Ractopamine, a livestock feed additive, is a full agonist at trace amine-associated receptor 1. J. Pharmacol. Exp. Ther., 350: 124-129. [Crossref] [PubMed] [PMC]
3. Onishchenko, G.G., Popova, A., Tutel'ian, V.A., Zaitseva, N.V., Khotimchenko, S.A., Gmoshinskii, I.V., Sheveleva, S.A., Rakitskii, V.N., Shur, P.Z., Lisitsyn, A.B. and Kir'ianov, D.A. (2013) About the human health safety estimation of ractopamine intake together with the food. Vest. Ross. Akad. Med. Nauk, 6: 4-8. [Crossref]
4. Centner, T.J., Alvey, J.C. and Stelzleni, A.M. (2014) Beta-agonists in livestock feed: Status, health concerns, and international trade. J. Anim. Sci., 92: 4234-4240. [Crossref]
5. Guddat, S., FuBholler, G., Geyer, H., Thomas, A., Braun, H., Haenelt, N., Schwenke, A., Klose, C., Thevis, M. and Schanzer, W. (2012) Clenbuterol-regional food contamination a possible source for inadvertent doping in sports. Drug Test. Anal., 4: 534-538. [Crossref] [PubMed]
6. Li, L., Tang, C., Zhang, J., Zhao, Q. and Zhang, K. (2016) The potential of various living tissues for monitoring clenbuterol abuse in food-producing Chinese Simmental beef cattle. J. Anal. Toxicol., 40: 72-77. [PubMed]
7. Sakai, N., Sakai, M., Haron, D.E., Yoneda, M. and Mohd, M.A. (2016) Beta-agonist residues in cattle, chicken and swine livers at the wet market and the environmental impacts of wastewater from livestock farms in Selangor State, Malaysia. Chemosphere, 165: 183-190. [Crossref] [PubMed]
8. Groot, M.J., Lasaroms, J.J., Van Bennekom, E.O., Van Hende, J. and Nielen, M.W. (2013) Possible contamination with clenbuterol from treated veal calves to untreated pen mates. Food Additives Contaminants. A Chem. Anal. Control Expos. Risk Assess., 30: 1063-1067. [Crossref] [PubMed]
9. Guo, P., Luo, Z., Xu, X., Zhou, Y., Zhang, B., Chang, R., Du, W., Chang, C. and Fu, Q. (2017) Development of molecular imprinted column-on line-two dimensional liquid chromatography for selective determination of clenbuterol residues in biological samples. Food Chem., 217: 628-636. [Crossref]
10. Parr, M.K., Blokland, M.H., Liebetrau, F., Schmidt, A.H., Meijer, T., Stanic, M., Kwiatkowska, D., Waraksa, E. and Sterk, S.S. (2017) Distinction of clenbuterol intake from drug or contaminated food of animal origin in a controlled administration trial-the potential of enantiomeric separation for doping control analysis. Food Addit. Contam. A. Chem. Anal. Control Exposure Risk Assessment, 34: 525-535. [Crossref] [PubMed]
11. Lazuardi, M., Wahyudi, M.T. and Munier, R.S. (2013) Re-evaluate interrelationship dose-response of diminazene aceturate against to infected mice of Trypanosoma Evansi Bangkalan isolates. J. Vet., 14: 173-177.
12. Lazuardi, M. (2016) Bagian Umum Ilmu Farmasi Veteriner. Ghalia Indonesia Press, Jakarta, Indonesia.
13. Giannetti, L., Ferretti, G., Gallo, V., Necci, F., Giorgi, A., Marini, F., Gennuso, E. and Neri, B. (2016) Analysis of beta-agonist residues in bovine hair: Development of a UPLC-MS/MS method and stability study. J. Chromatogr. B, 1036-1037: 76-83. [Crossref] [PubMed]
14. Lazuardi, M. and Bambang, H. (2016) LC ESI-MS and FT-IR analysis of Dendrophthoe pentandra L. Miq Leaf methanolic extracts to identify compounds with progesterone-like effects. Pak. J. Nutr., 15: 274-282. [Crossref]
15. Teotia, D., Saini, S.S., Gaid, M., Beuerle, T., Beerhues, L. and Sircar, D. (2016) Development and validation of a new HPLC method for the determination of biphenyl and dibenzofuran phytoalexins in Rosaceae. J. Chromatogr. Sci., 54: 918-922. [Crossref] [PubMed]
16. Lazuardi, M. and Bambang, H. (2017) High-performance liquid chromatography ultraviolet-photodiode array detection method for aflatoxin B(1) in cattle feed supplements. Vet. World, 10: 932-938. [Crossref] [PubMed] [PMC]
17. Yan, K., Zhang, H., Hui, W., Zhu, H., Li X., Zhong F., Tong, X. and Chen, C. (2016) Rapid screening of toxic salbutamol, ractopamine, and clenbuterol in pork sample by high-performance liquid chromatography-UV method. J. Food Drug Anal., 24: 277-283. [Crossref] [PubMed]
18. Poudel, A., Kim, S.G., Lamichhane, R., Kim, Y.K., Jo, H.K. and Jung, H.J. (2014) Quantitative assessment of traditional oriental herbal formulation Samhwangsasim-tang using UPLC technique. J. Chromatogr. Sci., 52: 176-185. [Crossref] [PubMed]
19. Asberg, D., Nilsson, M., Olsson, S., Samuelsson, J., Svensson, O., Klick, S., Ennis, J., Butterworth, P., Watt, D., Iliadou, S., Karlsson, A., Walker, J.T., Arnot, K., Ealer, N., Hernqvist, K., Svensson, K., Grinell, A., Quist, P.O., Karlsson, A. and Fornstedt, T. (2016) A quality control method enhancement concept-Continual improvement of regulatory approved QC methods. J. Pharm. Biomed. Anal., 129: 273-281. [Crossref] [PubMed]
20. Lazuardi, M., Restiadi, T.I. and Bambang, H. (2017) Calculated Withdrawal Time by Lazuardi Equation Method. In: Prosiding/Proceeding: Musyawarah Nasional ke III Asosiasi Farmakologi dan Farmasi Veteriner Indonesia = 3rd National Conference of Indonesia Veterinary Pharmacy and Pharmacology Association. P4IPVI, Surabaya. p41-43.
21. de Oliveira, M.A., Pires, F.R., Ferraco, M. and Belo, A.F. (2014) The validation of an analytical method for sulfentrazone residue determination in soil using liquid chromatography and a comparison of chromatographic sensitivity to millet as a bioindicator species. Molecules, 19: 10982-10997. [Crossref] [PubMed]
22. Zhao, Z., Yao, T., Qin, Y., Yang, X., Li, J., Li, J. and Gu, X. (2015) Clenbuterol distribution and residues in goat tissues after the repeated administration of a growth-promoting dose. J. Anal. Toxicol., 39: 465-471. [Crossref] [PubMed]
23. Andac, SC. (2016) Determination of drugs by online column-switching liquid chromatography. J. Chromatogr. Sci., 54: 1641-1647. [Crossref] [PubMed]
24. Knych, H.K., Mitchell, M.M., Steinmetz, S.J. and McKemie, D.S. (2014) Detection, pharmacokinetics and cardiac effects following administration of clenbuterol to exercised horses. Equine Vet. J., 46: 380-385. [Crossref] [PubMed]
25. Yang, Y.G., Song, L.X., Jiang, N., Xu, X.T., Di, X.H. and Zhang, M. (2015) Pharmacokinetics of ambroxol and clenbuterol tablets in healthy Chinese volunteers. Int. J. Clin. Exp. Med., 8: 18744-18750. [PubMed] [PMC]
26. Fernandez-Varon, E., Carceles-Garcia, C., Serrano-Rodriguez, J.M. and Carceles-Rodriguez, C.M. (2016) Pharmacokinetics (PK), pharmacodynamics (PD), and PK-PD integration of ceftiofur after a single intravenous, subcutaneous and subcutaneous-LA administration in lactating goats. BMC Vet. Res., 12: 232-242. [Crossref]
27. Lazuardi, M. and Sikumbang, R. (2010) Biofarmasetik dan Farmakokinetik Klinik Medis Veteriner. Ghalia Pressk, Jakarta, Indonesia.
28. Hsiao, P.F., Chang, S.K., Hsu, T.H., Li, K.P. and Chou, C.C. (2016) Pharmacokinetics and tissue depletion of doxycycline administered at high dosage to broiler chickens via the drinking water. Acta Vet. Hung., 64: 472-481. [Crossref] [PubMed]
29. Kissell, L.W., Leavens, T.L., Baynes, R.E., Riviere, J.E. and Smith, G.W. (2015) Comparison of pharmacokinetics and milk elimination of flunixin in healthy cows and cows with mastitis. J. Am. Vet. Med. Assoc., 246: 118-125. [Crossref] [PubMed]
30. Lust, E.B., Barthold, C., Malesker, M.A. and Wichman, T.O. (2011) Human health hazards of veterinary medications: Information for emergency departments. J. Emerg. Med., 40: 198-207. [Crossref] [PubMed]
31. Li, L., Zhang, J., Tang, C. and Zhao, Q. (2014) Accumulation of clenbuterol residues in the hair of Chinese Simmental beef cattle during and after treatment. J. Anal. Toxicol., 38: 52-56. [Crossref] [PubMed]
32. Spiller, H.A., James, K.J., Scholzen, S. and Borys, D.J. (2013) A descriptive study of adverse events from clenbuterol misuse and abuse for weight loss and bodybuilding. Substain. Abus., 34: 306-312. [Crossref] [PubMed]