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Two validated chromatographic determinations of an antifungal drug, its toxic impurities and degradation product: A comparative study.
Biomed Chromatogr 2019; 33(8):e4547BC

Abstract

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, H1 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 F254 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 C18 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.

Authors+Show Affiliations

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

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

30941788

Citation

Abdelaleem, Eglal A., et al. "Two Validated Chromatographic Determinations of an Antifungal Drug, Its Toxic Impurities and Degradation Product: a Comparative Study." Biomedical Chromatography : BMC, vol. 33, no. 8, 2019, pp. e4547.
Abdelaleem EA, Abdelrahman MM, Ali NW, et al. Two validated chromatographic determinations of an antifungal drug, its toxic impurities and degradation product: A comparative study. Biomed Chromatogr. 2019;33(8):e4547.
Abdelaleem, E. A., Abdelrahman, M. M., Ali, N. W., & Emam, R. A. (2019). Two validated chromatographic determinations of an antifungal drug, its toxic impurities and degradation product: A comparative study. Biomedical Chromatography : BMC, 33(8), pp. e4547. doi:10.1002/bmc.4547.
Abdelaleem EA, et al. Two Validated Chromatographic Determinations of an Antifungal Drug, Its Toxic Impurities and Degradation Product: a Comparative Study. Biomed Chromatogr. 2019;33(8):e4547. PubMed PMID: 30941788.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Two validated chromatographic determinations of an antifungal drug, its toxic impurities and degradation product: A comparative study. AU - Abdelaleem,Eglal A, AU - Abdelrahman,Maha M, AU - Ali,Nouruddin W, AU - Emam,Raghda A, Y1 - 2019/04/29/ PY - 2019/01/29/received PY - 2019/03/20/revised PY - 2019/03/29/accepted PY - 2019/4/4/pubmed PY - 2019/8/6/medline PY - 2019/4/4/entrez KW - HPTLC KW - RP-HPLC KW - stability indicating KW - tolnaftate KW - β-naphthol SP - e4547 EP - e4547 JF - Biomedical chromatography : BMC JO - Biomed. Chromatogr. VL - 33 IS - 8 N2 - 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, H1 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 F254 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 C18 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. SN - 1099-0801 UR - https://www.unboundmedicine.com/medline/citation/30941788/Two_validated_chromatographic_determinations_of_an_antifungal_drug_its_toxic_impurities_and_degradation_product:_A_comparative_study_ L2 - https://doi.org/10.1002/bmc.4547 DB - PRIME DP - Unbound Medicine ER -