(Ph. Eur. monograph 0901)
C17H22BrNO4 384.3 1944-12-3
Action and use
Beta2-adrenoceptor agonist; bronchodilator.
DEFINITION
5-[(1RS)-2-[(1RS)-2-(4-Hydroxyphenyl)-1-methylethyl]amino-1-hydroxyethyl]benzene-1,3-diol hydrobromide.
Content
99.0 per cent to 101.0 per cent (dried substance).
CHARACTERS
Appearance
White or almost white, crystalline powder.
Solubility
Soluble in water and in ethanol (96 per cent).
IDENTIFICATION
A. Infrared absorption spectrophotometry (2.2.24).
Comparison fenoterol hydrobromide CRS.
B. It gives reaction (a) of bromides (2.3.1).
TESTS
Solution S
Dissolve 2.00 g in carbon dioxide-free water R and dilute to 50.0 mL with the same solvent.
Appearance of solution
Solution S is clear (2.2.1) and not more intensely coloured than reference solution Y7 (2.2.2, Method II).
pH (2.2.3)
4.2 to 5.2 for solution S.
Related substances
Liquid chromatography (2.2.29). Prepare the solutions immediately before use.
Test solution: Dissolve 6.0 mg of the substance to be examined in water R and dilute to 5.0 mL with the same solvent.
Reference solution (a): Dilute 1.0 mL of the test solution to 25.0 mL with water R.
Reference solution (b): Dilute 2.5 mL of reference solution (a) to 100.0 mL with water R.
Reference solution (c): Dissolve the contents of a vial of fenoterol for system suitability CRS (containing impurities A, B and C) in 1 mL of water R.
Column:
— size: l = 0.15 m, Ø = 4.6 mm;
— stationary phase: end-capped octadecylsilyl silica gel for chromatography R (5 μm).
Mobile phase: Dissolve 24 g of anhydrous disodium hydrogen phosphate R in 1000 mL of water for chromatography R.
Mix 69 volumes of the solution and 1 volume of a 9 g/L solution of potassium dihydrogen phosphate R, adjust to pH 8.5 with phosphoric acid R and add 35 volumes of methanol R2.
Flow rate: 1.0 mL/min.
Detection: Spectrophotometer at 215 nm.
Injection: 20 μL.
Run time: 3 times the retention time of fenoterol.
Identification of impurities: Use the chromatogram supplied with fenoterol for system suitability CRS and the chromatogram obtained with reference solution (c) to identify the peaks due to impurities A, B and C.
Relative retention: With reference to fenoterol (retention time = about 7 min): impurity A = about 1.3; impurity B = about 2.0; impurity C = about 2.2.
System suitability: Reference solution (c):
— resolution: minimum 3.0 between the peaks due to fenoterol and impurity A; minimum 1.5 between the peaks due to impurities B and C.
Limits:
— correction factor: for the calculation of content, multiply the peak area of impurity B by 0.6;
— impurity A: not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (4.0 per cent);
— impurity C: not more than 3 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.3 per cent);
— impurity B: not more than twice the area of the principal peak in the chromatogram obtained with reference solution (b) (0.2 per cent);
— unspecified impurities: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (0.10 per cent);
— sum of impurities other than A: not more than 3 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.3 per cent);
— disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent).
Iron (2.4.9)
Maximum 10 ppm.
Dissolve the residue obtained in the test for sulfated ash in 2.5 mL of dilute hydrochloric acid R and dilute to 10 mL with water R.
Loss on drying (2.2.32)
Maximum 0.5 per cent, determined on 1.000 g by drying in an oven at 105 °C.
Sulfated ash (2.4.14)
Maximum 0.1 per cent, determined on 1.0 g.
ASSAY
Dissolve 0.600 g in 50 mL of water R and add 5 mL of dilute nitric acid R, 25.0 mL of 0.1 M silver nitrate and 2 mL of ferric ammonium sulfate solution R2. Shake and titrate with 0.1 M ammonium thiocyanate until an orange colour is obtained. Carry out a blank titration.
1 mL of 0.1 M silver nitrate is equivalent to 38.43 mg of C17H22BrNO4.
STORAGE
Protected from light.
IMPURITIES
Specified impurities A, B, C.
A. 5-[(1RS)-2-[(1SR)-2-(4-hydroxyphenyl)-1-methylethyl]amino-1-hydroxyethyl]benzene-1,3-diol,
B. 1-(3,5-dihydroxyphenyl)-2-[[(1RS)-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethan-1-one
C. 5-[(1RS)-2-[(1RS)-2-(4-hydroxy-3-methylphenyl)-1-methylethyl]amino-1-hydroxyethyl]benzene-1,3-diol.
