Quantitative determination of naftifine and its degradation products in medicines by HPLC with small-volume columns

INTRODUCTION. Naftifine medicinal products are widely used in medical practice to treat fungal infections. A key quality attribute of a naftifine medicinal product is the content of the active substance. It is essential to develop quantitative analytical procedures for the routine control of medicines with a particular focus on reducing time and costs.

AIM. This study aimed to update the analytical procedures for the quantitative determination of naftifine and its impurities in medicines by high-performance liquid chromatography (HPLC) with small-volume columns providing a reduction in assay time and reagent consumption.

MATERIALS AND METHODS. This study focused on the active substance naftifine and naftifine-based medicinal products, including a 1% naftifine alcohol solution and a 1% naftifine cream for cutaneous use. The solutions were analysed on Agilent 1200 Infinity and Agilent Infinity II 1290 liquid chromatography systems equipped with diode-array detectors and several chromatographic columns: XBridge Phenyl, 20×4.6 mm, 2.5 μm; XBridge Phenyl, 20×4.6 mm, 3.5 μm; and Acquity BEH Phenyl, 75×2.1 mm, 1.7 μm. The specificity of the analytical procedure was evaluated using spiking solutions of N-methyl-1-naphthalenemethylamine and cinnamaldehyde as well as naftifine solutions after chemical, thermal, and photolytic decomposition.

RESULTS. The authors identified the optimal non-toxic solvent (0.1% orthophosphoric acid solution) and demonstrated the applicability of different solvents to different dosage forms. Additionally, the selected analytical conditions included the following: 10 μg/mL naftifine solutions were chromatographed on an XBridge Phenyl column (20×4.6 mm; 2.5 μm) using a gradient of 0.1% perchloric acid and acetonitrile at an elution rate of 1 mL/min. The study showed that the selected detection wavelength of 254 nm provided the best signal-to-noise ratio for the naftifine peak. The reproducibility of the developed quantitative determination procedure was confirmed by validation in accordance with the current requirements of the State Pharmacopoeia of the Russian Federation. The specificity of the analytical procedure was shown by chromatographic analysis of the solvent, mobile phase, and solutions containing the main naftifine impurities. The validation study confirmed the linearity of the analytical procedure in the range of 80–120% (with a correlation coefficient of 0.995). During the accuracy validation, the recovery rate was 100.2%. The validation study demonstrated the robustness of the analytical procedure to minor changes in the chromatographic parameters. The naftifine retention time amounted to approximately 2 minutes.

CONCLUSIONS. The authors developed a selective and sensitive HPLC-based analytical procedure for the quantitative determination of naftifine in medicines. This analytical procedure provides for a reduction in assay time and reagent consumption, and its compliance with the validation acceptance criteria indicates its suitability and reproducibility.

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