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Two validated chromatographic determinations of an antifungal drug, its toxic impurities and degradation product: A comparative study
Author(s) -
Abdelaleem Eglal A.,
Abdelrahman Maha M.,
Ali Nouruddin W.,
Emam Raghda A.
Publication year - 2019
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.4547
Subject(s) - chemistry , chromatography , paraben , silica gel , high performance liquid chromatography , preservative , antifungal drug , antifungal , organic chemistry , medicine , dermatology
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 1 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 254 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 18 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.