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Pharmaceutics  2011 

Development and Validation of a Microbiological Agar Assay for Determination of Orbifloxacin in Pharmaceutical Preparations

DOI: 10.3390/pharmaceutics3030572

Keywords: orbifloxacin, fluoroquinolones, bioassay, validation

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Orbifloxacin is a fluoroquinolone with broad-spectrum antimicrobial activity, and belongs to the third generation of quinolones. Regarding the quality control of medicines, a validated microbiological assay for determination of orbifloxacin in pharmaceutical formulations has not as yet been reported. For this purpose, this paper reports the development and validation of a simple, sensitive, accurate and reproducible agar diffusion method to quantify orbifloxacin in tablet formulations. The assay is based on the inhibitory effect of orbifloxacin upon the strain of Staphylococcus aureus ATCC 25923 used as test microorganism. The results were treated statistically by analysis of variance and were found to be linear ( r = 0.9992) in the selected range of 16.0–64.0 μg/mL, precise with relative standard deviation (RSD) of repeatability intraday = 2.88%, intermediate precision RSD = 3.33%, and accurate (100.31%). The results demonstrated the validity of the proposed bioassay, which allows reliable orbifloxacin quantitation in pharmaceutical samples and therefore can be used as a useful alternative methodology for the routine quality control of this medicine.


[1]  Nakamura, S. Veterinary use of the new quinolones in Japa. Drugs 1995, 49, 152–158.
[2]  Matsumoto, S.; Nakai, M.; Yoshida, M.; Katae, H. A study of metabolites isolated from urine samples of pigs and calves administered orbifloxacin. J. Vet. Pharmacol. Ther. 1999, 22, 286–289.
[3]  Martinez, M.; McDermott, P.; Walker, R. Pharmacology of the fluoroquinolones: a perspective for the use in domestic animals. Vet. J. 2006, 172, 10–28.
[4]  Davis, J.L.; Papich, M.G.; Weingarten, A. The pharmacokinetics of orbifloxacin in the horse following oral and intravenous administration. J. Vet. Pharmacol. Ther. 2006, 29, 191–197.
[5]  Marín, P.; Fernández-Varón, E.; Escudero, E.; Vancraeynest, D.; Cárceles, C.M. Pharmacokinetic-pharmacodynamic integration of orbifloxacin in rabbits after intravenous, subcutaneous, and intramuscular administration. J. Vet. Pharmacol. Ther. 2008, 31, 77–82.
[6]  Scott, D.W.; Peters, J.; Miller, W.H. Efficacy of orbifloxacin tablets for the treatment of superficial and deep pyoderma due to Staphylococcus intermedius infection in dogs. Can. Vet. J. 2006, 47, 999–1002.
[7]  McKay, L.; Rose Crystal, D.S.; Matousek, J.L.; Schmeitzel, L.S.; Gibson, N.M.; Gaskin, J.M. Antimicrobial testing of selected fluoroquinolones against Pseudomonas aeruginosa isolated from canine otitis. J. Am. Anim. Hosp. Assoc. 2007, 43, 307–312.
[8]  Ganière, J.P.; Médaille, C.; Etoré, F. In vitro antimicrobial activity of orbifloxacin against Staphylococcus intermedius isolates from canine skin and ear infections. Res. Vet. Sci. 2004, 77, 67–71.
[9]  Haines, G.R.; Brown, M.P.; Gronwall, R.R.; Merritt, K.A.; Baltzley, L.K. Pharmacokinetics of orbifloxacin and its concentration in body fluids and in endometrial tissues of mares. Can. J. Vet. Res. 2001, 65, 181–187.
[10]  DiPersio, J.R.; Jones, R.N.; Barrett, T.; Doern, G.V.; Pfaller, M.A. Fluoroquinolone-resistant Moraxella catarrhalis in a patient with pneumonia: report from the SENTRY antimicrobial surveillance program. Diagn. Microbiol. Infect. Dis. 1998, 32, 131–135.
[11]  Grave, K.; Tanem, H. Compliance with short term oral antibacterial drug treatment in dogs. J. Small. Anim. Pract. 1999, 40, 158–162.
[12]  Rantala, M.; Holso, K.; Lillas, A.; Huovinen, P.; Kaartinen, L. Survey of condition-based prescribing of antimicrobial drugs for dogs at a veterinary teaching hospital. Vet. Rec. 2004, 155, 259–262.
[13]  Boerlin, P.; Wissing, A.; Aarestrup, F.M.; Frey, J.; Nicolet, J. Antimicrobial growth promoter ban and resistance to macrolides and vancomycin in enterococci from pigs. J. Clin. Microbiol. 2001, 39, 4193–4195.
[14]  Emborg, H.D.; Andersen, J.S.; Seyfarth, A.M.; Wegener, H.C. Relations between the consumption of antimicrobial growth promoters and the occurrence of resistance among Enterococcus faecium isolated from broilers. Epidemiol. Infect. 2004, 132, 95–105.
[15]  Morimura, T.; Ohno, T.; Matsukura, H.; Nobuhara, Y. Degradation kinetics of the new antibacterial fluoroquinolone derivative, orbifloxacin, in aqueous solution. Chem. Pharm. Bull. 1995, 43, 1052–1054.
[16]  Morimura, T.; Ohno, T.; Matsukura, H.; Nobuhara, Y. Photodegradation kinetics of the new antibacterial fluoroquinolone derivative, orbifloxacin, in aqueous solution. Chem. Pharm. Bull. 1995, 43, 1000–1004.
[17]  Morimura, T.; Nobuhara, Y.; Matsukura, H. Photodegradation products of a new antibacterial fluoroquinolone derivative, orbifloxacin, in aqueous solution. Chem. Pharm. Bull. 1997, 45, 373–377.
[18]  Matsumoto, S.; Takahashi, M.; Kitadai, N.; Katae, H. A study of metabolites isolated from the urine samples of cats and dogs administered orbifloxacin. J. Vet. Med. Sci. 1998, 60, 1259–1261.
[19]  Hung, S.-W.; Shih, C.-W.; Chen, B.-R.; Tu, C.-Y.; Ling, Y.-F.; Tsou, L.-T.; Ho, S.-P.; Wang, W.-S. A new detection technique for fluoroquinolone-conjugated proteins by high performance liquid chromatography with UV/fluorescence detectors. J. Food. Drug Anal. 2007, 15, 71–74.
[20]  García, M.A.; Solans, C.; Aramayona, J.J.; Rueda, S.; Bregante, M.A. Determination of orbifloxacin in rabbit plasma by high-performance liquid chromatography with fluorescence detection. J. Chromatogr. Sci. 1999, 37, 199–202.
[21]  Johnston, L.; Mackay, L.; Croft, M. Determination of quinolones and fluoroquinolones in fish tissue and seafood by high-performance liquid chromatography with electrospray ionisation tandem mass spectrometric detection. J. Chromatogr. A 2002, 982, 97–109.
[22]  Schneider, M.J.; Donoghue, D.J. Multiresidue analysis of fluoroquinolone antibiotics in chicken tissue using liquid chromatography-fluorescence-multiple mass spectrometry. J. Chromatogr. B 2002, 780, 83–92.
[23]  Schneider, M.J.; Donoghue, D.J. Multiresidue determination of fluoroquinolone antibiotics in eggs using liquid chromatography–fluorescence–mass spectrometry. Anal. Chim. Acta 2003, 483, 39–49.
[24]  Schneider, M.J.; Vázquez-Moreno, L.; Bermúdez-Almada, M.C.; Guardado, R.B.; Ortega-Nieblas, M. Multiresidue determination of fluoroquinolones in shrimp by liquid chromatography-fluorescence-mass spectrometry. J. AOAC Int. 2005, 88, 1160–1166.
[25]  Schneider, M.J.; Reyes-Herrera, I.; Donoghue, D.J. Evaluation of serum as a potential matrix for multiresidue determination of fluoroquinolone antibiotics in chicken using liquid chromatography-fluorescence-mass spectrometry. J. AOAC Int. 2007, 90, 1716–1723.
[26]  Marín, P.; Escudero, E.; Fernández-Varón, E.; Cárceles, C.M. Pharmacokinetics and milk penetration of orbifloxacin after intravenous, subcutaneous, and intramuscular administration to lactating goats. J. Dairy Sci. 2007, 90, 4219–4225.
[27]  Abd El-Aty, A.M.; Choi, J.H.; Ko, M.W.; Khay, S.; Goudah, A.; Shin, H.C.; Kim, J.S.; Chang, B.J.; Lee, C.H.; Shim, J.H. Approaches for application of sub and supercritical fluid extraction for quantification of orbifloxacin from plasma and milk: Application to disposition kinetics. Anal. Chim. Acta 2009, 631, 108–115.
[28]  Yamada, R.; Kozono, M.; Ohmori, T.; Morimatsu, F.; Kitayama, M. Simultaneous determination of residual veterinary drugs in bovine, porcine, and chicken muscle using liquid chromatography coupled with eletrospray ionization tandem spectrometry. Biosci. Biotechnol. Biochem. 2006, 70, 54–65.
[29]  Llorent-Martínez, E.J.; Ortega-Barrales, P.; Molina-Díaz, A.; Ruiz-Medina, A. Implementation of terbium-sensitized luminescence in sequential-injection analysis for automatic analysis of orbifloxacin. Anal. Bioanal. Chem. 2008, 392, 1397–1403.
[30]  Brazilian Pharmacopeial Convention. Brazilian Pharmacopoeia, 4rd ed. ed.; Atheneu: S?o Paulo, Brazil, 1988.
[31]  U.S. Pharmacopeial Convention. The U.S. Pharmacopeia, 34th ed. ed.; U.S. Pharmacopeial Convention: Rockville, MD, USA, 2011.
[32]  Hewitt, W. Microbiological Assay for Pharmaceutical Analysis: A Rational Approach; Interpharm/CRC Press: Boca Raton, FL, USA, 2003; pp. 97–115.
[33]  ICH. Harmonised Tripartite Guideline. Validation of Analytical Procedures: Text And Methodology — Q2(R1), In Proceedings of International Conference on Harmonisation, Geneva, The Switzerland, November 2005.
[34]  Marona, H.R.N.; Schapoval, E.E.S. Desarrollo de análisis microbiológico para la determinación de esparfloxacino en polvo y en comprimidos de 200 mg. Inf. Tecnol. 1998, 9, 151–154.
[35]  AOAC INTERNATIONAL. Official Methods of Analysis, 18th ed. ed.; AOAC INTERNATIONAL: Gaithersburg, MD, USA, 2005.
[36]  Gomes, G.C.; Salgado, H.R.N. Microbiological assay for determination of lomefloxacin in coated tablets. J. AOAC Int. 2006, 89, 1077–1079.
[37]  Salgado, H.R.N.; Lopes, C.C.G.O.; Lucchesi, M.B.B. Microbiological assay for gatifloxacin in pharmaceutical formulations. J. Pharm. Biom. Anal. 2006, 40, 443–446.
[38]  Moreno, A.R.; Salgado, H.R.N. Microbiological assay for ceftazidime injection. J. AOAC Int. 2007, 90, 1379–1382.
[39]  Tozo, G.C.G.; Salgado, H.R.N. Microbiological assay for cefoxitin sodium in dosage form. J. AOAC Int. 2007, 90, 452–455.
[40]  Baird, R.M.; Hodges, N.A.; Denyer, S.P. Handbook of Microbiological Quality Control: Pharmaceuticals and Medical Device; CRC Press: Boca Raton, FL, USA, 2000.


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