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Current Pharmaceutical Analysis

Editor-in-Chief

ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Research Article

Determination of Flunixin in Swine Plasma, Urine and Feces by UPLCMS/ MS and its Application in the Real Samples

Author(s): Zugong Yu*, Xiaoqing Luo, Fanxi Guo, Zhenrui Zhang and Lin Peng

Volume 15, Issue 1, 2019

Page: [51 - 60] Pages: 10

DOI: 10.2174/1573412913666170918163625

Price: $65

Abstract

Background: Flunixin is a Non-Steroidal Anti-Inflammatory Drug (NSAID), because it can effectively alleviate the organism of pyrexia, inflammation and pain, it has been widely used in veterinary practice. In order to better study flunixin in the body's absorbed, distributed, metabolized and excreted, our team developed a UPLC-MS/MS method for determination of flunixin in swine plasma, urine and feces.

Methods: Flunixin was extracted from the sample by liquid-liquid extraction and cleaned-up using a mixed-mode Oasis MCX solid-phase extraction column. Analysis was performed on UPLC-MS/MS operating in Multiple Reaction Monitoring (MRM) mode. Internal standard was used for quantitation of target drug.

Results: Recoveries of fortified samples ranged from 90.2% to 101.4%, with Relative Standard Deviations (RSD) lower than 17.0%. The Limits Of Detection (LODs) and Quantification (LOQs) in plasma were 0.25 and 0.5 µg L-1, in urine were 0.25 and 0.5 µg L-1, and in feces were 0.5 and 1 µg kg-1, respectively. This validated method was successfully applied to the determination of flunixin in real samples. The half-life of flunixin after the last dose in pigs was 7.37±1.60 h after intramuscular administration of 2.2 mg/kg of flunixin, and approximately 6.8% and 1.9% of the administered dose was excreted as parent compound in urine and feces respectively.

Conclusion: The developed UPLC-MS/MS method for determination of flunixin in swine plasma, urine and feces was validated and successfully applied to monitor flunixin from real samples.

Keywords: Flunixin, swine plasma, swine urine, swine feces, ultra-performance liquid chromatography-tandem mass spectrometry, metabolism.

Graphical Abstract
[1]
Kallings, P. Nonsteroidal anti-inflammatory drugs. Vet. Clin. N. Am-Equine., 1993, 9, 523-541.
[2]
Buur, J.L.; Baynes, R.E.; Smith, G.; Riviere, J.E. Pharmacokinetics of flunixin meglumine in swine after intravenous dosing. J. Vet. Pharmacol. Ther., 2006, 29(5), 437-440.
[3]
Meucci, V.; Vanni, M.; Sgorbini, M.; Odore, R.; Minunni, M.; Intorre, L. Determination of phenylbutazone and flunixin meglumine in equine plasma by electrochemical-based sensing coupled to selective extraction with molecularlyimprinted polymers. Sensor. Actuat. B. Chem., 2013, 179, 226-231.
[4]
Araujo, A.C.P.; Salvadori, M.C.; Velletri, M.E.; Camargo, M.M.A. Influence of furosemideon the detection of flunixin meglumine in horse urine samples. J. Anal. Toxicol., 1990, 14(3), 146-148.
[5]
Gu, X.; Meleka-Boules, M.; Chen, C.L.; Ceska, D.M.; Tiffany, D.M. Determination of flunixin in equine urine and serum by capillary electrophoresis. J. Chromatogr. B, 1997, 692, 187-198.
[6]
Johansson, M.; Anlér, E.L. Gas chromatographic analysis of flunixin in equineurine after extractive methylation. J. Chromatogr. B, 1988, 427, 55-66.
[7]
Asea, P.A.; Patterson, J.R.; Korsrud, G.O.; Dowling, P.M.; Boison, J.O. Determination of flunixin residues in bovine muscle tissue by liquid chromatography with UV detection. J. AOAC Int., 2001, 84, 659-665.
[8]
Abdelmonaim, A.; Beatriz, J.; Badredine, S.; Evaristo, B. Simultaneous determination of 20 pharmacologically active substances in cow’s milk, goat’s milk, and human breast milk by gas chromatography- mass spectrometry. J. Agr. Food Chem., 2011, 59(9), 5125-5132.
[9]
Jedziniak, P.; Szprengier-Juszkiewicz, T.; Olejnik, M.; Zmudzki, J. Determination of non-steroidal anti-inflammatory drugs residues in animal muscles by liquid chromatography-tandem mass spectrometry. Anal. Chim. Acta, 2010, 672, 85-92.
[10]
Luo, Y.; Rudy, J.A.; Uboh, C.E.; Soma, L.R.; Guan, F.; Enright, J.M.; Tsang, D.S. Quantification and confirmation of flunixin in equine plasma by liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. J. Chromatogr. B., 2004, 801, 173-184.
[11]
Commission Decision. 2002/657/EC, Off. J. Eur. Commun., L221, 2002 8.
[12]
Wasfi, I.A.; Hadi, A.A.A.; Alkatheeri, N.A.; Barezaiq, I.M. El- Ghazali, M.; Boni, N.S.; Zorob, O. Identification of a flunixin metabolite in camel by gas chromatography-mass spectrometry. J. Chromatogr. B, 1998, 709, 209-215.
[13]
Lee, C.D.; Maxwell, L.K. Effect of body weight on the pharmacokinetics of flunixin meglumine in miniature horses and quarter horses. J. Vet. Pharmacol. Ther., 2013, 37, 35-42.
[14]
Belal, F.F.; El-Razeq, S.A.A.; Fouad, M.M.; Fouad, F.A. Micellar high performance liquid chromatographic determination of flunixin meglumine in bulk, pharmaceutical dosage forms, bovine liver and kidney. Anal. Chem. Res., 2015, 3, 63-69.
[15]
Ho, E.N.M.; Leung, D.K.K.; Wan, T.S.M.; Yu, N.H. Comprehensive screening of anabolic steroids, corticosteroids, and acidic drugs in horse urine by solid-phase extraction and liquid chromatography- mass spectrometry. J. Chromatogr. A, 2006, 1120, 38-53.
[16]
Hilton, H.G.; Magdesian, K.G.; Groth, A.D.; Knych, H.; Stanley, S.D.; Hollingsworth, S.R. Distribution of flunixin meglumine and firocoxib into aqueous humor of horses. J. Vet. Intern. Med., 2011, 25, 1127-1133.
[17]
Popot, M.A.; Donval, A.; Bonnaire, Y.; Huau, J. Use of accelerating solvent extraction for Detecting non-steroidal anti-inflammatory drugs in horse feces. J. Anal. Toxicol., 2006, 30(5), 323-330.
[18]
Horii, Y.; Ikenaga, M.; Shimoda, M.; Kokue, E. Pharmacokinetics of flunixin in the cat: Enterohepatic circulation and active transport mechanism in the liver. J. Vet. Pharmacol. Ther., 2004, 27, 65-69.
[19]
Wasfi, I.A.; Boni, N.S.; Hadi, A.A.A.; Elghazali, M.; Zorob, O.; Alkatheeri, N.A.; Barezaiq, I.M. Pharmacokinetics, metabolism and urinary detection time of flunixin after intravenous administration in camels. J. Vet. Pharmacol. Ther., 1998, 21, 203-208.
[20]
Dubreil-Chéneau, E.; Pirotais, Y.; Bessiral, M.; Roudaut, B.; Verdon, E. Development and validation of a confirmatory method for the determination of 12 non steroidal anti-inflammatory drugs in milk using liquid chromatography-tandem mass spectrometry. J. Chromatogr. A, 2011, 1218, 6292-6301.
[21]
Cheng, Z.; McKellar, Q.; Nolan, A. Pharmacokinetic studies of flunixin meglumine and phenylbutazone in plasma, exudate and transudate in sheep. J. Vet. Pharmacol. Ther., 1998, 21, 315-321.
[22]
Gallo, P.; Fabbrocino, S.; Vinci, F.; Fiori, M.; Danese, V.; Serpe, L. Confirmatory identification of sixteen non-steroidal antiinflammatory drug residues in raw milk by liquid chromatography coupled with ion trap mass spectrometry. Rapid Commun. Mass Sp., 2008, 22, 841-854.
[23]
Peng, T.; Yu, J.; Yan, M.; Li, X.J.; Chen, D.D.; Dai, H.H.; Guo, W.; Li, S.J.; Tang, Y.Z. Simultaneous determination of residues of non-steroidal anti-inflammatory drugs in swine liver by ultraperformance liquid chromatographywith electrospray ionization quadrupole rods tandem mass spectrometric detection. Chinese . J. Anal. Chem., 2009, 3, 363-368.
[24]
Zhu, A.L.; Peng, T.; Liu, L.; Xia, X.; Hu, T.; Tao, X.Q.; Wen, K.; Cheng, L.L.; Li, J.C.; Ding, S.Y.; Cao, X.Y.; Jiang, H.Y. Ultraperformance liquid chromatography-tandem massspectrometry determination and depletion profile of flunixin residues in tissues after single oral administration in rabbits. J. Chromatogr. B., 2013, 934, 8-15.
[25]
Waxman, S.J.; Kukanich, B.; Milligan, M.; Beard, W.L.; Davis, E.G. Pharmacokinetics of Concurrently administered intravenous lidocaine and flunixin in healthy horses. J. Vet. Pharmacol. Ther., 2011, 35, 413-416.
[26]
Hu, T.; Peng, T.; Li, X.J.; Chen, D.D.; Dai, H.H.; Zhou, Y.N.; Xia, X.; Ding, S.Y.; Zhu, A.L.; Jiang, H.Y. Ion exchange solid phase extraction coupled with liquid chromatography tandem mass spectrometry for determination of 8 classes of non-steroidal antiinflammatory drugs residues in animal tissues. Chinese . J. Anal. Chem., 2012, 2, 236-242.

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