View More View Less
  • 1 Department of Chemistry, PRRM College of Pharmacy, Kadapa, Andhra Pradesh, India
  • 2 Department of Chemistry, JNTUA College of Engineering, Pulivendula, Y.S.R (Kadapa), Andhra Pradesh, India
  • 3 Jawaharlal Nehru Technological University Anantapur Oil Technology Research Institute, Anantapur, Andhra Pradesh, India
  • 4 Department of Chemistry, College of Pharmacy, Mother Theresa Post Graduate & Research Institute of Health Sciences, Gorimedu, Puducherry, India
Restricted access

Summary

The objective of the current study is to develop a validated specific stability-indicating isocratic reversed-phase liquid chromatographic method for the quantitative determination of levofloxacin and its related substances in pharmaceutical dosage forms in the presence of degradation products and its process-related impurities. Forced degradation studies were performed on levofloxacin as per the International Conference on Harmonisation (ICH)-prescribed stress conditions using acid, base, oxidative, water hydrolysis, thermal stress and photolytic degradation to show the stability-indicating power of the method. Significant degradation was observed during oxidative stress; minor degradation was observed in acidic stress and no degradation was observed in other stress conditions. The chromatographic method was optimized using the samples generated from forced degradation studies and the spiked impurity solution. The analysis was carried out with a 50 mm length × 4.6 mm i.d., 3.0 μm particle size YMC Pack Pro-C18 column using the mobile phase consisting of a mixture of 1.0% (v/v) triethylamine in water with pH adjusted to 6.30, using orthophosphoric acid, methanol and acetonitrile (7.7:1.3:1.0) pumped at a flow rate of 0.8 mL min−1 with ultraviolet (UV) detection at 235 nm. The limit of detection and the limit of quantification for the levofloxacin and its process-related impurities were established. The stressed test solutions were assayed against the qualified working standard of levofloxacin and the mass balance in each case was in between 99.1% and 99.9%, indicating that the developed liquid chromatography (LC) method was a stability-indicating technique. Validation of the developed LC method was carried out as per ICH requirements.

  • [1]. J. Gore Z. Bryant M.D. Stone M. Nollmann N.R. Cozzarelli C. Bustamante 2006 Nature 439 100104.

  • [2]. A.H. Arteseros J. Barbosa R. Companó 2002 J. Chromatogr. A 45 124.

  • [3]. V. Lorian 1996 Antibiotics in Laboratory Medicine 4th edn Williams and Wilkins Baltimore 591592.

  • [4]. V.F. Samanidou C.E. Demetriou I.N. Papadoyannis 2003 Anal. Bioanal. Chem. 375 623629.

  • [5]. S. Siewert 2006 J. Pharm. Biomed. Anal. 41 360362.

  • [6]. F.A. Wong S.J. Juzwinand S.C. Flor 1997 J. Pharm. Biomed. Anal. 15 765771.

  • [7]. X. Gao G. Yao N. Guo F. An X. Guo 2007 Drug Discov. Ther. 1 136140.

  • [8]. M. Lalitha Devi K.B. Chandrasekhar 2009 J. Pharm. Biomed. Anal. 50 710717.

  • [9]. M. Saeed Arayne N. Sultana F.A. Siddiqui 2007 Pak. J. Pharm. Sci. 20 100106.

  • [10]. S.N. Meyyanathan G.V.S. Ramasarma B. Suresh 2007 J. Sep. Sci. 54 991995.

  • [11]. J.E. Conte Jr. J.A. Golden M. McIver E. Zurlinden 2006 Int. J. Antimicrob. Agents 28 114121.

  • [12]. International Conference on Harmonization (ICH), IFPMA, Geneva, 2006.

  • [13]. ICH, Validation of Analytical Procedures: Text and Methodology, Q2 (R1), Geneva, 2005.