Clean, safe and fast method by HPLC for quantification of rifaximin-based samples

Kogawa A. C., Peltonen L., Salgado H. R. N., Chorilli M.

Keywords: rifaximin-based samples, HPLC, analytical method validation, quality control, pharmaceutical analysis.

Abstract: Rifaximin, is an oral antimicrobial drug, belongs to Class IV, according to the Biopharmaceutic Classification System, and has low solubility and permeability. Three rifaximin-based samples were developed by complexation to β-cyclodextrin using phase solubility diagram and malaxation, and decreasing particle size using wet milling. The effectiveness of preparation of new rifaximin-based samples has been previously confirmed and characterized by thermal and spectroscopic techniques, but the quantification of rifaximin has not yet been performed because there is no method available. So an ecologically correct method by HPLC was developed and validated to evaluate the rifaximin content in them. The analysis was performed using a C18 column, water with 0.1% glacial acetic acid and ethanol (52:48, v/v) as mobile phase, 0.9 mL min-1, 290 nm, and 25°C. The method proved to be linear in the range of 5-50 μg mL-1 and precise with relative standard deviations of 1.15% for intra-day and 0.47% for inter-day precision. Accuracy was confirmed by standard recovery with mean recoveries between 100.99 and 101.32%. The method was robust to small changes in wavelength and temperature used, purified water source, the proportion of ethanol and acetic acid in the mobile phase and flow. Selectivity was confirmed by the evaluation of possible interferences and forced degradation tests in acidic, basic, oxidative, neutral, and photolytic media and it proved to be indicative of stability. The method also involves characteristics of green Analytical Chemistry for a pharmaceutical analysis: it does not use toxic organic solvents, it is fast (approximately 5 minutes), and waste generation is low.

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