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Volume 2 - Sep 2013
Orbifloxacin (ORBI) was subjected to different ICH (Q1A(R2)) prescribed stress conditions of thermal stress, hydrolysis, oxidation and photolysis. It was stable to dry heat (60 ÂºC) and photolysis (UV-VIS) in solid form. It showed extensive decomposition under hydrolytic and photolytic conditions in acid, base and neutral solutions. Degradation was also observed in oxidative condition. Degradation products of ORBI formed under different forced conditions were characterized through LCâ€“MS studies. In total, eleven major degradation products (DP1-DP11) were detected. Successful separation of drug and degradation products formed under various stress conditions was achieved on a analytical column SymmetryShield Waters RP18, 5 Âµm, 250 x 4.6 mm using 5% acetic acid and methanol as mobile phase in a gradient mode at flow rate of 0.5 ml/min. The peaks were detected using a PDA detector set at 290 nm. The method was extended to LCâ€“APCI-MS for characterization of the degradation products and the pathways of decomposition were proposed.
Orbifloxacin, Chemistry degradation, SIAM, LC-APCI-MS, Stability
- Bonfilio, R, Cazedey, E.C.L., AraÃºjo, M.B., Salgado, H.R.N., 2012. Analytical validation of quantitative high-performance liquid chromatographic methods in pharmaceutical analysis: a practical approach. Crit. Rev. Anal. Chem. 42, 87â€“100.
- British Pharmacopoeia, 2011. Her Majestyâ€™s Stationery Office, London. v.1, pp.88âˆ’90.
- Cazedey, E.C.L., Othman, A., Garg, S., Salgado, H.R.N., 2011. A validated stabilityâˆ’indicating LC method for orbifloxacin in the presence of degradation products. Curr. Pharmaceut. Anal. 7, 176âˆ’181.
- Davis, J.L., Papich, M.G., Weingarten, A., 2006. The pharmacokinetics of orbifloxacin in the horse following oral and intravenous administration. J. Vet. Pharmacol. Ther. 29, 191â€“197.
- GaniÃ¨re, J.P., MÃ©daille, C., EtorÃ©, F., 2004. In vitro antimicrobial activity of orbifloxacin against Staphylococcus intermedius isolates from canine skin and ear infections. Res. Vet. Sci. 77, 67-71.
- Goudah, A., Aboâˆ’Elâˆ’Sooud, K., 2008. Pharmacokinetics and milk penetration of orbifloxacin after intravenous and intramuscular injections to dromedary lactating camels (Camelus dromedaries). J. Vet. Pharmacol. Ther. 31, 276âˆ’280.
- Haines, G.R., Brown, M.P., Gronwall, R.R., Merritt, K.A., Baltzley, L.K., 2001. Pharmacokinetics of orbifloxacin and its concentration in body fluids and in endometrial tissues of mares. Can. J. Vet. Res. 65, 181â€“187.
- ICH, Guidelines on impurities in new drug products, in: Proceeding of International Conference on Harmonization, IFPMA, Geneva, 2006b.
- ICH, Guidelines on impurities in new drug substances, in: Proceeding of International Conference on Harmonization, IFPMA, Geneva, 2006a.
- ICH, Validation of Analytical Procedures: Text and Methodology, International Conference on Harmonization, IFPMA, Geneva, 2005.
- Ihrke, P.J., Papich, M.G., Demanuelle, T.C., 1999. The use of fluoroquinolones in veterinary dermatology. Vet. Dermatol. 10, 193-204.
- MarÃn, P., Escudero, E., FernÃ¡ndez-VarÃ³n, E., CÃ¡rceles, C.M., 2007. Pharmacokinetics and milk penetration of orbifloxacin after intravenous, subcutaneous, and intramuscular administration to lactating goats. J. Dairy Sci. 90, 4219â€“4225.
- MarÃn, P., FernÃ¡ndez-VarÃ³n, E., Escudero, E., Vancraeynest, D., CÃ¡rceles, C.M., 2008. Pharmacokinetic-pharmacodynamic integration of orbifloxacin in rabbits after intravenous, subcutaneous, and intramuscular administration. J. Vet. Pharmacol. Ther. 31, 77â€“82.
- Martinez, M., Mcdermott, P., Walker, R., 2006. Pharmacology of the fluoroquinolones: a perspective for the use in domestic animals. Vet. J. 172, 10â€“28.
- Matsumoto, S., Nakai, M., Yoshida, M., Katae, H., 1999. A study of metabolites isolated from urine samples of pigs and calves administered orbifloxacin. J. Vet. Pharmacol. Ther. 22, 286-289.
- Matsumoto, S., Takahashi, M., Kitadai, N., Katae, H., 1998. A study of metabolites isolated from the urine samples of cats and dogs administered orbifloxacin. J. Vet. Med. Sci. 60, 1259-1261.
- Mckay, L., Rose Crystal, D.S., Matousek, J.L., Schmetizel, L.S., Gibson, N.M., Gaskin, J.M., 2007. Antimicrobial testing of selected fluoroquinolones against Pseudomonas aeruginosa isolated from canine otitis. J. Am. Anim. Hosp. Assoc. 43, 307â€“312
- Morimura, T., Kohno, K., Nobuhara, Y., Matsukura, H., 1997b. Photoreaction and active oxygen generation by photosensitization of a new antibacterial fluoroquinolone derivative, orbifloxacin, in the presence of chloride ion. Chem. Pharm. Bull. 45, 1828âˆ’1832
- Morimura, T., Nobuhara, Y., Matsukura, H., 1997a. Photodegradation products of a new antibacterial fluoroquinolone derivative, orbifloxacin, in aqueous solution. Chem. Pharm. Bull. 45, 373-377
- Morimura, T., Ohno, T., Matsukura, H., Nobuhara, Y., 1995a. Degradation kinetics of the new antibacterial fluoroquinolone derivative, orbifloxacin, in aqueous solution. Chem. Pharm. Bull. 43, 1052-1054
- Morimura, T., Ohno, T., Matsukura, H., Nobuhara, Y., 1995b. Photodegradation kinetics of the new antibacterial fluoroquinolone derivative, orbifloxacin, in aqueous solution. Chem. Pharm. Bull. 43, 1000-1004
- Nakamura, S., 1995. Veterinary use of the new quinolones in Japan. Drugs 49, 152â€“158
- Oâ€™neil, M.J. (Ed.), 2006. The Merck index: an encyclopedia of chemicals, drugs and biologicals, 14th. ed. Merck & Co., Whitehouse Station (NJ). pp. 1182
- Rang, H.P., Dale, M.M., Ritter, J.M., Moore, P.K., 2003. Pharmacology, 5th ed. Churchill Livingstone, London
- Reynolds, J.E.F. (Ed), 2007. Martindale the extra pharmacopoeia, 35th.ed. Pharmaceutical Press, London. pp. 278
- Scott, D.W., Peters, J., Miller Jr, W.H., 2006. Efficacy of orbifloxacin tablets for the treatment of superficial and deep pyoderma due to Staphylococcus intermedius infection in dogs. Can. Vet. J. 47, 999â€“1002
- Stability testing of new drug substances and products, QIA (R2), in: Proceeding of International Conference on Harmonization (ICH), IFPMA, Geneva, 2003
- United States Pharmacopeia, 2011. The United States Pharmacopeial Convention, 34th ed. Rockville, MD. pp. 3732âˆ’3734
- Zivanovic, Lj., Zigic, G., Zecevic, M., 2006. Investigation of chromatographic conditions for the separation of ofloxacin and its degradation products. J. Chrom. A 1119, 224â€“230
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