Universal Response Method for the Quantitative Analysis of Photodegradation Impurities in Lomefloxacin Hydrochloride Ear Drops by Liquid Chromatography Coupled with Charged Aerosol Detector.

In terms of risk assessment especially for the impurities with different ultraviolet responses, quantitative analysis without the availability of corresponding reference substances currently poses a challenge. In this study, a universal response method was established for the quantitative analysis of photodegradable impurities in lomefloxacin hydrochloride ear drops by high performance liquid chromatography-charged aerosol detector (HPLC-CAD) for the first time. The chromatographic conditions and CAD parameters were optimized for a good separation and sensitivity. The uniform response of developed method was validated by impurity reference substances with different ultraviolet responses. In the gradient compensation HPLC-CAD method validation, good linearities were obtained with coefficient of determination (R2) all greater than 0.999 for lomefloxacin and impurity reference substances. The average recoveries of the impurities were 98.63%- 102.18% by UV and 97.92%- 102.57% by CAD, respectively. RSDs all were less than 2.5% for intra-day and inter-day precision by UV and CAD, with good precision and accuracy. The correction factor experimental results showed that the developed method provided a uniform response to the impurities with differences chromophores in lomefloxacin. The effects of packaging materials and excipients on the photodegradation were also investigated using the developed method. The results of correlation analysis showed that the packaging materials with low light transmittance and the organic excipients (glycerol and ethanol) could significantly improve the stability of lomefloxacin hydrochloride ear drops. The developed HPLC-CAD quantification method was a reliable and universal response method for quantitative analysis of impurities in the lomefloxacin. This study also revealed the key factors affecting the photodegradation of lomefloxacin hydrochloride ear drops, which guided enterprises to improve drug prescription and packaging materials and ensure the public medication safety.