A validated stability-indicating isocratic LC method for levofloxacin in the presence of degradation products and its process-related impurities

Abstract

The objective of the current study is to develop a validated specific stabilityindicating 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.

An integrated approach for detection and characterization of the trace impurities in levofloxacin using liquid chromatography-tandem mass spectrometry

“…[19,20] Because of the various structural features, IMPs and DPs pose risks to patients and compromise the quality of the drug. In the references available to determine and/or identify impurities of levofloxacin, LC methods had been described to control the impurities of levofloxacin by relative retention time, [21][22][23][24][25][26] and LC-MS was used to identify the major DPs. [22,26] Three IMPs and four major DPs of levofloxacin were reported, [21,22,26,27] while the analysis of the trace impurities in levofloxacin is still challenging.…”