| Synonyms | 3,n-dimethylaniline, 3-methylamino toluene, aniline, n,m-dimethyl, benzenamine, n,3-dimethyl, m,n-dimethylaniline, m-toluidine, n-methyl, n-3-dimethylbenzenamine, n-methyl-3-methylaniline, n-methyl-3-toluidine, n-methyl-m-toluidine
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| Reference | [1]. Biomed Chromatogr. 2019 Aug;33(8):e4547. doi: 10.1002/bmc.4547. Epub 2019 Apr 29.<br />
Two validated chromatographic determinations of an antifungal drug, its toxic impurities and degradation product: A comparative study.<br />
Abdelaleem EA(1), Abdelrahman MM(1), Ali NW(1), Emam RA(1).<br />
Author information: (1)Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Al shaheed Shehata Ahmed Hegazy st., 62514, Beni-Suef, Egypt.<br />
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.<br />
DOI: 10.1002/bmc.4547 PMID: 30941788 [Indexed for MEDLINE]<br />
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[2]. Spectrochim Acta A Mol Biomol Spectrosc. 2019 Dec 5;223:117290. doi: 10.1016/j.saa.2019.117290. Epub 2019 Jun 19.<br />
Novel spectral manipulations for determinations of Tolnaftate along with related toxic compounds: Drug profiling and a comparative study.<br />
Emam RA(1), Abdelrahman MM(2), Abdelaleem EA(2), Ali NW(2).<br />
Author information: (1)Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Beni-Suef University, Alshaheed Shehata Ahmed Hegazy st., 62514 Beni-Suef, Egypt. Electronic address: [email protected]. (2)Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Beni-Suef University, Alshaheed Shehata Ahmed Hegazy st., 62514 Beni-Suef, Egypt.<br />
A comparative study using novel quadruple divisor and mean centering of ratio spectra spectrophotometric methods was developed for resolution of five- component mixture of Tolnaftate, β-naphthol (Tolnaftate alkaline degradation product and its toxic impurity), methyl(m-tolyl)carbamic acid (Tolnaftate alkaline degradation product), N-methyl-m-toluidine (Tolnaftate toxic impurity) and methyl paraben (as a preservative). For the novel quadruple divisor method, each component in the quinary mixture was determined by dividing the quinary mixture spectrum by a sum of standard spectrum of equal concentration of the other four components as a quadruple divisor. First derivative of each ratio spectra was then obtained which allowed selective determination of each component without interference from other components in the mixture. The second method was mean centering of ratio spectra that depended on utilizing the mean centered ratio spectra in four successive steps leading to enhancement of the signal to noise ratio. The absorption spectra of the five studied components were recorded in the wavelength range of 210-350 nm. The mean centered fourth ratio spectra amplitudes for each component were used for its determination. The developed methods were successfully applied for determination of laboratory prepared quinary mixtures to ensure method's specificity, then, were further applied on Tinea Cure® cream where no interference from excipients. For the first time, Tolnaftate was determined along with its toxic impurity; β-naphthol, that could be absorbed by the skin, causing systemic toxic effects, unlike Tolnaftate that poorly absorbed, indicating the significance of this work. The proposed methods were statistically compared with each other and with the reference method. Furthermore, ICH guidelines were followed for their validation.<br />
DOI: 10.1016/j.saa.2019.117290 PMID: 31284238 [Indexed for MEDLINE]<br />
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[3]. Fresenius J Anal Chem. 2000 May;367(1):91-3. doi: 10.1007/s002160051606.<br />
Assay of tolnaftate and related impurities by isocratic supercritical fluid chromatography.<br />
Patil ST(1), Bhoir IC, Bhagwat AM, Sundaresan M.<br />
Author information: (1)C.B. Patel Research Centre for Chemistry and Biological Sciences, Mumbai, India.<br />
Tolnaftate, an antifungal drug (TF) and related impurities arising from synthesis, viz., N-methyl-m-toluidine (NMmT) and beta-naphthol-1-chlorothio carbamate (beta-NCTC) can be determined by supercritical fluid chromatography. Even though it was possible to elute TF completely with neat SCF CO2, the peaks of the impurities were found to merge. The chromatographic figures of merit of the three analytes such as retention time (tR), capacity factor (k), selectivity factor (alpha), no. of theoretical plates (N), were optimized. The three compounds can be resolved in 5 min on a Hypersil (250 x 4.0 mm) 5 mu, C18 column with supercritical carbon dioxide, modified with 1.96% methanol as the mobile phase at 9.81 MPa and at 40 degrees C. Detection was carried out at 220 nm. The data as evaluated by the linear regression least squares fit method gave linearity ranges from 0.2 to 10.0 microg/mL for TF and NMmT and 0.3 to 10.0 microg/mL for beta-NCTC with correlation coefficients > 0.99. The method was successfully employed to estimate levels of 0.01% for NMmT and 0.02% for beta-NCTC with respect to TF.<br />
DOI: 10.1007/s002160051606 PMID: 11227443 [Indexed for MEDLINE]
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