(Ph. Eur. monograph 1615)
C23H36N2O2 372.6 98319-26-7
Action and use
5-Alpha reductase inhibitor; treatment of benign prostatic hyperplasia.
Preparation
Finasteride Tablets
DEFINITION
N-(1,1-Dimethylethyl)-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide.
Content
98.0 per cent to 102.0 per cent (dried substance).
CHARACTERS
Appearance
White or almost white, crystalline powder.
Solubility
Practically insoluble in water, freely soluble in anhydrous ethanol and in methylene chloride.
It shows polymorphism (5.9).
IDENTIFICATION
Infrared absorption spectrophotometry (2.2.24).
Comparison: finasteride CRS.
If the spectra obtained in the solid state show differences, dissolve the substance to be examined and the reference substance separately in methanol R, evaporate to dryness and record new spectra using the residues.
TESTS
Specific optical rotation (2.2.7)
+ 12.0 to + 14.0 (dried substance).
Dissolve 0.250 g in methanol R and dilute to 25.0 mL with the same solvent.
Related substances
Liquid chromatography (2.2.29).
Solvent mixture acetonitrile R1, water for chromatography R (50:50 V/V).
Test solution (a): Dissolve 25.0 mg of the substance to be examined in the solvent mixture and dilute to 50.0 mL with the solvent mixture.
Test solution (b): Dissolve 100.0 mg of the substance to be examined in the solvent mixture and dilute to 10.0 mL with the solvent mixture.
Reference solution (a): Dissolve 25.0 mg of finasteride CRS in the solvent mixture and dilute to 50.0 mL with the solvent mixture.
Reference solution (b): Dissolve 10 mg of finasteride for peak identification CRS (containing impurities A and C) in 1.0 mL of the solvent mixture.
Reference solution (c): Dilute 1.0 mL of test solution (b) to 100.0 mL with the solvent mixture. Dilute 1.0 mL of this solution to 10.0 mL with the solvent mixture.
Column:
— size: l = 0.25 m, Ø = 4.0 mm;
— stationary phase: base-deactivated end-capped octadecylsilyl silica gel for chromatography R (5 μm);
— temperature: 60 °C.
Mobile phase: acetonitrile R1, tetrahydrofuran R, water for chromatography R (10:10:80 V/V/V).
Flow rate: 1.5 mL/min.
Detection: Spectrophotometer at 210 nm.
Injection: 15 μL of test solution (b) and reference solutions (b) and (c).
Run time: Twice the retention time of finasteride.
Identification of impurities Use the chromatogram supplied with finasteride for peak identification CRS and the chromatogram obtained with reference solution (b) to identify the peaks due to impurities A and C.
Relative retention: With reference to finasteride (retention time = about 28 min): impurity A = about 0.9; impurity C = about 1.3.
System suitability:
— signal-to-noise ratio: minimum 40 for the principal peak in the chromatogram obtained with reference solution (c);
— peak-to-valley ratio: minimum 5, where Hp = height above the baseline of the peak due to impurity A and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to finasteride in the chromatogram obtained with reference solution (b).
Calculation of percentage contents:
— correction factor: multiply the peak area of impurity A by 2.4;
— for each impurity, use the concentration of finasteride in reference solution (c).
Limits:
— impurities A, C: for each impurity, maximum 0.3 per cent;
— unspecified impurities: for each impurity, maximum 0.10 per cent;
— total: maximum 0.5 per cent;
— reporting threshold: 0.05 per cent.
Loss on drying (2.2.32)
Maximum 0.5 per cent, determined on 1.000 g by drying in an oven at 105 °C.
ASSAY
Liquid chromatography (2.2.29) as described in the test for related substances with the following modification.
Injection: Test solution (a) and reference solution (a).
Calculate the percentage content of C23H36N2O2 taking into account the assigned content of finasteride CRS.STORAGE
Protected from light.
IMPURITIES
Specified impurities A, C.
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) B.
A. N-(1,1-dimethylethyl)-3-oxo-4-aza-5α-androstane-17β-carboxamide (dihydrofinasteride),
B. methyl 3-oxo-4-aza-5α-androst-1-ene-17β-carboxylate,
C. N-(1,1-dimethylethyl)-3-oxo-4-azaandrosta-1,5-diene-17β-carboxamide
