Edition: BP 2025 (Ph. Eur. 11.6 update)
C19H17NOS 307.4 2398-96-1
Action and use
Antifungal.
DEFINITION
O-Naphthalen-2-yl methyl(3-methylphenyl)carbamothioate.
Content
97.0 per cent to 103.0 per cent (dried substance).
CHARACTERS
Appearance
White or yellowish-white powder.
Solubility
Practically insoluble in water, freely soluble in acetone and in methylene chloride, very slightly soluble in ethanol (96 per cent).
IDENTIFICATION
Infrared absorption spectrophotometry (2.2.24).
Comparison tolnaftate CRS.
TESTS
Impurity D
Liquid chromatography (2.2.29).
Test solution Dissolve 0.400 g of the substance to be examined in 2 mL of methylene chloride R. Extract with 3 quantities, each of 3 mL, of 0.01 M hydrochloric acid. Combine the aqueous phases and dilute to 10.0 mL with 0.01 M hydrochloric acid.
Reference solution (a) Dissolve 20.0 mg of N-methyl-m-toluidine R (impurity D) in 50.0 mL of methylene chloride R.
Reference solution (b) Dilute 1.0 mL of reference solution (a) to 100.0 mL with methylene chloride R. Take 2.0 mL of this solution and extract with 3 quantities, each of 3 mL, of 0.01 M hydrochloric acid. Combine the aqueous phases and dilute to 10.0 mL with 0.01 M hydrochloric acid.
Reference solution (c) Dissolve 10 mg of the substance to be examined in 25 mL of methanol R. Add 2 mL of this solution to 2 mL of reference solution (a) and dilute to 25 mL with methanol R.
Column:
— size: l = 0.15 m, Ø = 4.6 mm;
— stationary phase: octadecylsilyl silica gel for chromatography R (5 μm).
Mobile phase:
— mobile phase A: trifluoroacetic acid R, methanol R, water R (0.1:10:90 V/V/V);
— mobile phase B: trifluoroacetic acid R, water R, methanol R (0.1:10:90 V/V/V);
| Time
(min) |
Mobile phase A
(per cent V/V) |
Mobile phase B
(per cent V/V) |
| 0 – 3
3 – 8 8 – 20 |
70
70 → 0 0 |
30
30 → 100 100 |
Flow rate 1.0 mL/min.
Detection Spectrophotometer at 254 nm.
Injection 100 μL of the test solution and reference solution (b); 10 μL of reference solution (c).
Relative retention With reference to tolnaftate (retention time = about 15 min): impurity D = about 0.25.
System suitability:
— resolution: minimum 5.0 between the peaks due to impurity D and tolnaftate in the chromatogram obtained with reference solution (c);
— symmetry factor: maximum 1.9 for the peak due to impurity D in the chromatogram obtained with reference solution (b).
Limit:
— impurity D: not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (20 ppm).
Related substances
Liquid chromatography (2.2.29).
Test solution Dissolve 25 mg of the substance to be examined in 5 mL of methanol R and dilute to 25.0 mL with the same solvent.
Reference solution (a) Dilute 1.0 mL of the test solution to 100.0 mL with methanol R. Dilute 1.0 mL of this solution to 10.0 mL with methanol R.
Reference solution (b) Dissolve 5 mg of tolnaftate for system suitability CRS (containing resolution component A) in 5.0 mL of methanol R.
Column:
— size: l = 0.15 m, Ø = 4.6 mm;
— stationary phase: octadecylsilyl silica gel for chromatography R (5 μm).
Mobile phase:
— mobile phase A: trifluoroacetic acid R, water R, methanol R (0.1:30:70 V/V/V);
— mobile phase B: trifluoroacetic acid R, water R, methanol R (0.1:10:90 V/V/V);
| Time
(min) |
Mobile phase A
(per cent V/V) |
Mobile phase B
(per cent V/V) |
| 0 – 12
12 – 30 30 – 33 |
100
100 → 0 0 |
0
0 → 100 100 |
Flow rate 1.0 mL/ min.
Detection Spectrophotometer at 254 nm.
Injection 10 μL.
Relative retention With reference to tolnaftate (retention time = about 18 min): resolution component A = about 0.7.
System suitability Reference solution (b):
— resolution: minimum 5.0 between the peaks due to resolution component A and tolnaftate.
Limits:
— unspecified impurities: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.10 per cent);
— total: not more than twice the area of the principal peak in the chromatogram obtained with reference solution (a) (0.2 per cent);
— disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent).
Loss on drying (2.2.32)
Maximum 0.5 per cent, determined on 1.000 g by drying at 60 °C at a pressure not exceeding 0.7 kPa for 3 h.
Sulfated ash (2.4.14)
Maximum 0.1 per cent, determined on 1.0 g.
ASSAY
Dissolve 50.0 mg in methanol R and dilute to 250.0 mL with the same solvent. Dilute 2.0 mL of this solution to 50.0 mL with methanol R. Measure the absorbance (2.2.25) at the absorption maximum at 257 nm.
Calculate the content of C19H17NOS taking the specific absorbance to be 720.
STORAGE
Protected from light.
IMPURITIES
Specified impurities D.
Other detectable impurities (the following substances would, if present at a sufficient level, be detected by one or other of the tests in the monograph. They are limited by the general acceptance criterion for other/unspecified impurities and/or by the general monograph Substances for pharmaceutical use (2034). It is therefore not necessary to identify these impurities for demonstration of compliance. See also 5.10. Control of impurities in substances for pharmaceutical use) A, B.
A. naphthalen-2-ol (β-naphthol),
B. O,O-dinaphthalen-2-yl carbonothioate,
D. N,3-dimethylaniline (N-methyl-m-toluidine).
