AAPS PharmSciTech

, Volume 15, Issue 6, pp 1588–1597 | Cite as

Photodegradation of Moxifloxacin in Aqueous and Organic Solvents: A Kinetic Study

  • Iqbal Ahmad
  • Raheela Bano
  • Syed Ghulam Musharraf
  • Sofia Ahmed
  • Muhammad Ali Sheraz
  • Qamar ul Arfeen
  • Muhammad Salman Bhatti
  • Zufi Shad
Research Article


The kinetics of photodegradation of moxifloxacin (MF) in aqueous solution (pH 2.0–12.0), and organic solvents has been studied. MF photodegradation is a specific acid-base catalyzed reaction and follows first-order kinetics. The apparent first-order rate constants (k obs) for the photodegradation of MF range from 0.69 × 10−4 (pH 7.5) to 19.50 × 10−4 min−1 (pH 12.0), and in organic solvents from 1.24 × 10−4 (1-butanol) to 2.04 × 10−4 min−1 (acetonitrile). The second-order rate constant (k 2) for the [H+]-catalyzed and [OH]-catalyzed reactions are 6.61 × 10−2 and 19.20 × 10−2 M−1 min−1, respectively. This indicates that the specific base-catalyzed reaction is about three-fold faster than that of the specific acid-catalyzed reaction probably as a result of the rapid cleavage of diazabicyclononane side chain in the molecule. The k obs-pH profile for the degradation reactions is a V-shaped curve indicating specific acid-base catalysis. The minimum rate of photodegradation at pH 7–8 is due to the presence of zwitterionic species. There is a linear relation between k obs and the dielectric constant and an inverse relation between k obs and the viscosity of the solvent. Some photodegraded products of MF have been identified and pathways proposed for their formation in acid and alkaline solutions.


acid-base catalysis kinetics moxifloxacin photodegradation rate–pH profile solvent effect 


  1. 1.
    Sweetman SC. The complete drug reference. 36th ed. London: Pharmaceutical Press; 2009. p. 302.Google Scholar
  2. 2.
    British Pharmacopoeia. Monograph on moxifloxacin. London: Her Majesty’s Stationary Office; 2013. Electronic version.Google Scholar
  3. 3.
    O’Neil MJ. The Merck Index. 15th ed. Cambridge: The Royal Society of Chemistry; 2013. p. 1171.Google Scholar
  4. 4.
    Appelbaum PC, Hunter PA. The fluoroquinolone antibacterials: past, present and future perspective. Int J Antimicrob Agents. 2000;16:5–15.PubMedCrossRefGoogle Scholar
  5. 5.
    Eliopulos GM. Activity of newer fluoroquinolones in vitro against gram-positive bacteria. Drugs. 1999;58:23–8.CrossRefGoogle Scholar
  6. 6.
    Sharma SK, George N, Kdhiravan T, Saha PK, Mishra HK, Hanif M. Prevalence of extensively drug resistant tuberculosis among patients with multidrug-resistant tuberculosis: a retrospective hospital-based study. Indian J Med Res. 2009;130:392–5.PubMedGoogle Scholar
  7. 7.
    Soni K. Fluoroquinolones: chemistry & action—a review. Indo Glob J Pharm Sci. 2012;2:43–53.Google Scholar
  8. 8.
    Maruri F, Sterling TR, Kaiga AW, Blackman A, Vander Heigden YF, Mayer C, et al. A systematic review of gyrase mutations associated with fluoroquinolone-resistant Mycobacterium tuberculosis and a propose gyrase numbering system. J Antimicrob Chemother. 2012;67:819–31.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Tarkase KN, Admane SS, Sonkhede NG, Shejwal SR. Development and validation of UV spectrophotometric methods for determination of moxifloxacin HCl in bulk and pharmaceutical formulations. Der Pharma Chemica. 2012;4:1180–5.Google Scholar
  10. 10.
    De Guidi G, Giuffrida S, Monti S, Pisu PS, Sortino S, Costanzo LL. Molecular mechanism of phtosensitization induced by drugs XIV: two different behaviors in the photochemistry and photosensitization of antibacterials containing a fluoroquinolone like chromophore. Int J Photoenergy. 1999;1:1–6.CrossRefGoogle Scholar
  11. 11.
    Viola G, Facciola L, Canton M, Vedaldi D, Acqua FD, Aloisi GG, et al. Photophysical and phototoxic properties of the antibacterial fluoroquinolones levofloxacin and moxifloxacin. Chem Biodivers. 2004;1:782–800.PubMedCrossRefGoogle Scholar
  12. 12.
    Hidalgo ME, Pessoa C, Fernandez E, Cardenas AM. Comparative determination 232 of photodegradation kinetics of quinolones. J Photochem Photobiol A Chem. 1993;73:135–8.CrossRefGoogle Scholar
  13. 13.
    Burhenne J, Ludwig M, Spiteller M. Polar photodegradation products of quinolones determined by HPLC/MS/MS. Chemosphere. 1999;38:1279–86.CrossRefGoogle Scholar
  14. 14.
    Kummerer K. Antibiotics in the aquatic environment—a review—part I. Chemosphere. 2009;75:417–34.PubMedCrossRefGoogle Scholar
  15. 15.
    United States Pharmacopoeia 30–National Formulary 25. Rockville, MD, USA: United States Pharmacopoeial Convention, Inc., Electronic version; 2007.Google Scholar
  16. 16.
    Lorenzo F, Navaratnam S, Edge R, Allen NS. Primary photophysical properties of moxifloxacin—a fluoroquinolone antibiotic. Photochem Photobiol. 2008;84:1118–25.PubMedCrossRefGoogle Scholar
  17. 17.
    Doorslaer XV, Demeestere K, Heynderickx PM, Langenhove HV, Dewulf J. UV-A and UV-C induced photolytic and photocatalytic degradation of aqueous ciprofloxacin and moxifloxacin: reaction kinetics and role of adsorption. Appl Catal B Environ. 2011;101:540–7.CrossRefGoogle Scholar
  18. 18.
    Sturini M, Speltini A, Maraschi F, Profumo A, Pretali L, Irastorza EA, et al. Photolytic and photocatalytic degradation of fluoroquinolones in untreated river water under natural sunlight. Appl Catal B Environ. 2012;119–120:32–9.CrossRefGoogle Scholar
  19. 19.
    Hubicka U, Zmudzki P, Talik P, Zuromska BW, Krzek J. Photodegradation assessment of ciprofloxacin, moxifloxacin, norfloxacin and ofloxacin in the presence of excipients from tablets by UPLC-MS/MS and DSC. J Chem Cent. 2013;7:1–12.CrossRefGoogle Scholar
  20. 20.
    Torniainen K, Tammilehto S, Ulvi V. The effect of pH, buffer type and drug concentration on the photodegradation of ciprofloxacin. Int J Pharm. 1996;132:53–61.CrossRefGoogle Scholar
  21. 21.
    Burhenne J, Ludwig M, Nikoloudis P, Spiteller M. Photolytic degradation of fluoroquinolone carboylic acid in aqueous solution. Part I: primary photoproducts and halflives. Environ Sci Pollut Res. 1997;4:10–5.CrossRefGoogle Scholar
  22. 22.
    Burhenne J, Ludwig M, Spiteller M. Photolytic degradation of fluoroquinolone carboylic acid in aqueous solution. Part II: isolation and structural elucidation of polar photometabolities. Environ Sci Pollut Res. 1997;4:61–7.CrossRefGoogle Scholar
  23. 23.
    Lovdahl MJ, Priebe SR. Characterization of clinafloxacin photodegradation products by LC-MS/MS andNMR. J Pharm Biomed Anal. 2000;23:521–34.PubMedCrossRefGoogle Scholar
  24. 24.
    Salgado HRN, Moreno PRH, Braga AL, Schapoval EES. Photodegradation of sparfloxacin 259 and isolation of its degradation products by preparative HPLC. Rev Cienc Farm Basica Apl. 2005;26:47–54.Google Scholar
  25. 25.
    Motwani SK, Khar RK, Ahmad FJ, Chopra S, Kohli K, Talegaonkar S, et al. Stability indicating high performance thin-layer chromatographic determination of gatifloxacin as bulk drug and form polymeric nanoparticles. Anal Chim Acta. 2006;576:253–60.PubMedCrossRefGoogle Scholar
  26. 26.
    Budai M, Grof P, Zimmer A, Papai K, Klebovich I, Ludanyi K. UV light induced photodegradation of liposomes encapsulated fluoroquinolones. J Photochem Photobiol A Chem. 2008;198:268–73.CrossRefGoogle Scholar
  27. 27.
    Wang J, Li W, Li C-G, Hu Y-Z. Photodegradation of fleroxacin injection: different products with different concentration levels. AAPS PharmSciTech. 2011;12:872–8.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Ahmad I, Bano R, Sheraz MA, Ahmed S, Mirza T, Ansari SA. Photodegradation of levofloxacin in aqueous and organic solvents: a kinetic study. Acta Pharma. 2013;63:221–7.Google Scholar
  29. 29.
    Hutchinson DJ, Johnson CE, Klein KC. Stability of extemporaneously prepared moxifloxacin oral suspensions. Am J Health Syst Pharm. 2009;66:665–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Kumar MT, Srikanth G, Rao JV, Rao KS. Development and validation of HPLC-UV method for the estimation of levofloxacin in human plasma. Int J Pharm Pharm Sci. 2011;3:247–50.Google Scholar
  31. 31.
    Rama Subbaiah P, Kumudhavalli MV, Saravanan C, Kumar M, Chandira RM. Method development and validation for estimation of moxifloxacin HCl in tablet dosage form by RP-HPLC method. Pharm Anal Acta. 2010;1:1–2.Google Scholar
  32. 32.
    Sultana N, Arayne MS, Akhtar M, Shamim S. High-performance liquid chromatography assay for moxifloxacin in bulk, pharmaceutical formulations and serum: application to in-vitro metal interactions. J Chin Chem Soc. 2010;57:1–10.Google Scholar
  33. 33.
    Dewani AP, Barik BB, Kanungo SK, Wattyani BR, Chandewar AV. Development and validation of RP-HPLC method for the determination of moxifloxacin in presence of its degradation products. Am-Eurasian J Sci Res. 2011;6:192–200.Google Scholar
  34. 34.
    Kunagu VS, Janardhan M. Development and validation of stability-indicating RP-HPLC method for estimation of moxifloxacin in moxifloxacin HCl tablets. Int J Pharm Invent. 2012;2:24–33.Google Scholar
  35. 35.
    Wang N, Zhu L, Zhao X, Yang W, Sun H. Improved HPLC method for the determination 285 of moxifloxacin in application to a pharmacokinetics study in patients with infectious diseases. ISRN Pharmacol. 2013;2013:1–7.Google Scholar
  36. 36.
    Motwani SK, Khar RK, Ahmad FJ, Chopra S, Kohli K, Talegaonkar S. Application of a validated stability indicating densitometric thin-layer chromatographic method to stress degradation studies on moxifloxacin. Anal Chim Acta. 2007;582:75–82.PubMedCrossRefGoogle Scholar
  37. 37.
    Devi ML, Chandrasekhar KB. A validated, specific stability-indicating RP-LC method for moxifloxacin and its related substances. Chromatographia. 2009;69:993–9.CrossRefGoogle Scholar
  38. 38.
    Hatchard CG, Parker CA. A new sensitive chemical actinometer. II. Potassium ferrioxalate as a standard chemical actinometer. Proc R Soc Lond A. 1956;235:518–36.CrossRefGoogle Scholar
  39. 39.
    Ahmed S, Sheraz MA, Yorucu C, Rehman IU. Quantitative determination of tolfenamic acid and its pharmaceutical formulation using FTIR and UV spectrometry. Cent Eur J Chem. 2013;11:1533–41.CrossRefGoogle Scholar
  40. 40.
    Finholt P, Jurgensen G, Kristiansen H. Catalytic effect of buffers on degradation of penicillin G in aqueous solution. J Pharm Sci. 1965;54:387–93.PubMedCrossRefGoogle Scholar
  41. 41.
    Connors KA, Amidon CL, Stella VJ, editors. Chemical stability of pharmaceuticals: a hand book for pharmacists. 2nd ed. New York: Wiley; 1986. p. 198–207. 250–256.Google Scholar
  42. 42.
    Zia H, Teharan M, Zargarbashi R. Kinetics of carbenicillin degradation in aqueous solution. Can J Pharm Sci. 1974;9:112–7.Google Scholar
  43. 43.
    Schwartz MA, Bara E, Rubycz I, Granatek AP. Stability of methacillin. J Pharm Sci. 1965;54:149–50.PubMedCrossRefGoogle Scholar
  44. 44.
    Maulding HV, Nazareno JP, Pearson JE, Michaelis AF. Practical kinetics III: benzodiazepine hydrolysis. J Pharm Sci. 1975;64:278–84.PubMedCrossRefGoogle Scholar
  45. 45.
    Mollica JA, Rehm CR, Smith JB, Govan HK. Hydrolysis of benzothiadiazines. J Pharm Sci. 1971;57:1380–4.CrossRefGoogle Scholar
  46. 46.
    Notari RE, Caiola SM. Catalysis of streptovitacin A dehydration: kinetics and mechanism. J Pharm Sci. 1969;58:1203–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Garrett ER, Seyda K. Prediction of stability in pharmaceutical preparations XX: stability evaluation and bioanalysis of cocaine and benzoylecgonine by high performance liquid chromatography. J Pharm Sci. 1983;72:258–71.PubMedCrossRefGoogle Scholar
  48. 48.
    Notari RE, Chin ML, Wittebort R. Arabinosylcytosine stability in aqueous solution: 313 pH profile and shelf life productions. J Pharm Sci. 1972;61:1189–96.PubMedCrossRefGoogle Scholar
  49. 49.
    Hamilton-Miller JMT. The effect of pH and of temperature on the stability and bioactivity of nystatin and amphotericin B. J Pharm Pharmacol. 1973;25:401–7.PubMedCrossRefGoogle Scholar
  50. 50.
    Notari RE, DeYoung JL. Kinetics and mechanisms of degradation of the antileukemic agent 5-azacytidine in aqueous solution. J Pharm Sci. 1975;64:1148–57.PubMedCrossRefGoogle Scholar
  51. 51.
    Langlois M-H, Montagut M, Dubost J-P, Grellet J, Saux M-C. Protonation equilibrium and lipophilicity of moxifloxacin. J Pharm Biomed Anal. 2005;37:389–93.PubMedCrossRefGoogle Scholar
  52. 52.
    Lemaire S, Tulkens PM, Bambeke FV. Contrasting effects of acidic pH on the extracellular and intracellular activities of the anti-gram-positive flouroquinolones moxifloxacin and delafloxacin against Staphylococcus aureus. Antimicrob Agents Chemother. 2011;55:649–58.PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Nangia A, Lam F, Hung CT. A stability of aqueous solution of norfloxacin. Drug Dev Ind Pharm. 1991;17:681–94.CrossRefGoogle Scholar
  54. 54.
    Hubicka U, Krzek J, Zuromska B, Walczak M, Zylewski M, Pawlowski D. Determination of photostability and photodegradation products of moxifloxacin in the presence of metal ions in solutions and solid phase. Kinetics and identification of photoproducts. Photochem Photobiol Sci. 2012;11:351–7.PubMedCrossRefGoogle Scholar
  55. 55.
    Park HR, Kim TH, Bark KM. Physicochemical properties of quinolone antibiotics in various environments. Eur J Med Chem. 2002;37:443–60.PubMedCrossRefGoogle Scholar
  56. 56.
    Ahmad I, Tollin G. Solvent effects on flavin electron transfer reactions. Biochemistry. 1981;20:5925–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Ahmad I, Fasihullah Q, Vaid FHM. Photolysis of formylmethylflavin in aqueous and organic solvents. Photochem Photobiol Sci. 2006;5:680–5.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2014

Authors and Affiliations

  • Iqbal Ahmad
    • 1
  • Raheela Bano
    • 1
  • Syed Ghulam Musharraf
    • 2
  • Sofia Ahmed
    • 1
  • Muhammad Ali Sheraz
    • 1
  • Qamar ul Arfeen
    • 2
  • Muhammad Salman Bhatti
    • 2
  • Zufi Shad
    • 1
  1. 1.Baqai Institute of Pharmaceutical SciencesBaqai Medical UniversityKarachiPakistan
  2. 2.H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological SciencesUniversity of KarachiKarachiPakistan

Personalised recommendations