Two validated chromatographic determinations of an antifungal drug, its toxic impurities and degradation product: A comparative study.

Biomed Chromatogr 2019 Aug 29;33(8):e4547. Epub 2019 Apr 29.

Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Al shaheed Shehata Ahmed Hegazy st., 62514, Beni-Suef, Egypt.

Tolnaftate, a thionoester anti-fungal drug, was subjected to alkaline hydrolysis to produce methyl(m-tolyl)carbamic acid and β-naphthol (tolnaftate impurity A). N-Methyl-m-toluidine, tolnaftate impurity D, was synthesized and structurally elucidated along with tolnaftate alkaline degradation products using IR, H NMR and MS. Two stability-indicating HPTLC and RP-HPLC methods were developed and validated, for the first time, for determination of tolnaftate, its alkaline degradation products and toxic impurities in the presence of methyl paraben, as a preservative in Tinea Cure cream. The proposed HPTLC method depended on separation of the studied components on TLC silica gel F plates using hexane-glacial acetic acid (8:2, v/v) as a developing system and scanning wavelength of 230 nm. The proposed RP-HPLC method was based on separation of the five components on an Eclipse plus C column. The mobile phase used was acetonitrile-water containing 1% ammonium formate (40:60, v/v), with a flow rate of 1 mL/min and detection wavelength of 230 nm. The proposed methods allowed the assay of tolnaftate toxic impurities, β-naphthol and N-methyl-m-toluidine, down to 2%, allowing tracing of β-naphthol that could be absorbed by the skin causing systemic toxic effects, unlike tolnaftate, indicating the high significance of such determination. International Conference on Harmonization guidelines were followed for validation.

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August 2019
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