Four simple, accurate, sensitive and low cost spectrophotometric methods have been developed and validated for the determination of lomefloxacin hydrochloride in the presence of its decarboxylated degradation product without preliminary separation. Method (I) is simultaneous equation method, while method (II), method (III) and method (IV) are ratio spectra manipulating methods, called ratio derivative, ratio difference and mean centering methods, respectively. Complete degradation of the drug and the degradation pathway was confirmed using TLC, IR, 1 H NMR and mass spectrometry. Calibration graphs were established in the range of 1-13μg/ml with good correlation coefficients. The developed methods were validated according to the International Conference on Harmonization (ICH) guidelines demonstrating good accuracy and precision. The results were statistically compared with those obtained by the reported method applying student's t-test and F-test at 95% confidence level and no significant difference was found.