DOI QR코드

DOI QR Code

Development and Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of ε-Acetamidocaproic Acid in Rat Plasma

  • 투고 : 2013.08.14
  • 심사 : 2013.09.16
  • 발행 : 2013.09.30

초록

A simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of ${\varepsilon}$-acetamidocaproic acid (AACA), the primary metabolite of zinc acexamate (ZAC), in rat plasma by using normetanephrine as an internal standard. Sample preparation involved protein precipitation using methanol. Separation was achieved on a Gemini-NX $C_{18}$ column ($150mm{\times}2.0mm$, i.d., 3 ${\mu}m$ particle size) using a mixture of 0.1% formic acid-water : acetonitrile (80 : 20, v/v) as the mobile phase at a flow rate of 200 ${\mu}l/min$. Quantification was performed on a triple quadrupole mass spectrometer employing electrospray ionization and operating in multiple reaction monitoring (MRM) and positive ion mode. The total chromatographic run time was 4.0 min, and the calibration curves of AACA were linear over the concentration range of 20~5000 ng/ml in rat plasma. The coefficient of variation and relative error at four QC levels were ranged from 1.0% to 5.8% and from -8.4% to 6.6%, respectively. The present method was successfully applied for estimating the pharmacokinetic parameters of AACA following intravenous or oral administration of ZAC to rats.

키워드

참고문헌

  1. Banos, J.E. and Bulbena, O. (1989) Zinc compounds as therapeutic agents in peptic ulcer. Methods Find. Exp. Clin. Pharmacol., 11, 117-122.
  2. Escolar, G. and Bulbena, O. (1989) Zinc compounds, a new treatment in peptic ulcer. Drugs Exp. Clin. Res., 15, 83-89.
  3. Escolar, G., Navarro, C., Sendros, S. and Bulbena, O. (1987) Effect of cold-restraint stress and zinc acexamate on gastric mucus production in intact glands. Arch. Int. Pharmacodyn. Ther., 290, 128-137.
  4. Guilarte Lopez-Manas, J., Valenzuela Barranco, M., Caballero Plasencia, A.M. and Martin Ruiz, J.L. (1998) [Endoscopic, histologic and morphometric evaluation of the gastric mucosa in patients with osteoarthritis treated with piroxicam and zinc acexamate]. Gastroenterol. Hepatol., 21, 212-217.
  5. Navarro, C., Escolar, G., Bravo, M.L., Jimenez, E. and Bulbena, O. (1990) Effect of zinc acexamate and raniditine on chronic gastric lesions in the rat. Digestion, 45, 121-129. https://doi.org/10.1159/000200233
  6. Bulbena, O., Escolar, G., Navarro, C., Bbravo, L. and Pfeiffer, C.J. (1993) Gastroprotective effect of zinc acexamate against damage induced by nonsteroidal antiinflammatory drugs; A morphological study. Dig. Dis. Sci., 38, 730-739. https://doi.org/10.1007/BF01316807
  7. Pfeiffer, C.J., Bulbena, O., Esplugues, J.V., Escolar, G., Navarro, C. and Esplugues, J. (1987) Anti-ulcer and membrane stabilizing actions of zinc acexamate. Arch. Int. Pharmacodyn. Ther., 285, 148-157.
  8. Esplugues, J.V., Bulbena, O., Escolar, G., Marti-Bonmati, E. and Esplugues, J. (1985) Effects of zinc acexamate on gastric mucosal resistance factors. Eur. J. Pharmacol., 109, 145-151. https://doi.org/10.1016/0014-2999(85)90415-7
  9. Navarro, C., Bravo, M.L., Carulla, C. and Bulbena, O. (1994) Gastrotoxic activity and inhibitory effects on gastric mucosal PGE2 production with different non-steroidal anti-inflammatory drugs: modifications induced by pretreatment with zinc acexamate. Prostaglandins Leukot. Essent. Fatty Acids, 50, 305-310. https://doi.org/10.1016/0952-3278(94)90238-0
  10. Yamaguchi, M. (2010) Role of nutritional zinc in the prevention of osteoporosis. Mol. Cell. Biochem., 338, 241-254. https://doi.org/10.1007/s11010-009-0358-0
  11. Daoudal, P., Boillot, A., Berthout, P., Bourgeois, F. and Barale, F. (1979) [So-called refractory hypoxemia: treatment with acexamic acid]. Nouv. Presse Med., 8, 3899.
  12. Uchiyama, S. and Yamaguchi, M. (2003) Alteration in serum and bone component findings induced in streptozotocin-diabetic rats is restored by zinc acexamate. Int. J. Mol. Med., 12, 949-954.
  13. Yamaguchi, M., Goto, M., Uchiyama, S. and Nakagawa, T. (2008) Effect of zinc on gene expression in osteoblastic MC3T3-E1 cells: enhancement of Runx2, OPG, and regucalcin mRNA expressions. Mol. Cell. Biochem., 312, 157-166. https://doi.org/10.1007/s11010-008-9731-7
  14. Guillard, O., Masson, P., Piriou, A., Brugier, J.C. and Courtois, P. (1987) Comparison of the anti-inflammatory activity of sodium acexamate and zinc acexamate in healing skin wounds in rabbits. Pharmacology, 34, 296-300. https://doi.org/10.1159/000138282
  15. Lacy, C., Armstrong, L., Goldman, M. and Lance, L. (2004) Drug Information Handbook. Lexi-Comp, Hudson, pp. 646-648.
  16. Musso, C.G., Enz, P., Mendoza, L., Sosa, A., Galimberti, R., Imperiali, N. and Algranati, L. (2006) Topical treatment of peritoneal catheter-related exit-site granuloma with acetamidohexanoic acid combined with gentamicin. Peritoneal Dial. Int., 26, 505-506.
  17. Thomson, J.M., Turner, L. and Poller, L. (1973) Inhibition of gastric plasmin acrivity by epsilon-aminocaproic acid. Ann. R. Coll. Surg. Engl., 53, 340-347.
  18. Choi, Y.H., Lee, U., Suh, J.H., Kim, Y.G., Choi, E.Y., Oh, E. and Lee, M.G. (2010) Pharmacokinetics and first-pass effects of $\varepsilon$-acetamidocaroic acid after administration of zinc acexamate in rats. Xenobiotica, 40, 485-498. https://doi.org/10.3109/00498251003774745
  19. Choi, Y.H., Lee, U., Suh, J.H., Kim, Y.G., Lee, M., Oh, E. and Lee, M.G. (2011) Pharmacokinetic interaction between $\varepsilon$-acetamidocaroic acid (AACA) and cimetidine in indomethacininduced acute gastric ulcer and control rats: inhibition of active renal secretion of AACA by cimetidine. Xenobiotica, 41, 409-415. https://doi.org/10.3109/00498254.2010.549250
  20. Roth, J.S., Kelley, J.A., Chun, H.G. and Ward, F.T. (1994) Simultaneous measurement of the cell-differentiating agent hexamethylene bisacetamide and its metabolites by gas chromatography. J. Chromatogr., 652, 149-159. https://doi.org/10.1016/0378-4347(93)E0395-7
  21. Lagerstedt, S.A., O'Kane, D.J. and Singh, R.J. (2004) Measurement of plasma free metanephrine and normetanephrine by liquid chromatography-tandem mass spectrometry for diagnosis of pheochromocytoma. Clin. Chem., 50, 603-611. https://doi.org/10.1373/clinchem.2003.024703