This document describes tests to analyze the purity of the pharmaceutical compound fenoterol hydrobromide. It provides specifications for 7 tests: appearance of solution, pH, related substances analysis by liquid chromatography, infrared absorption spectrophotometry, thin-layer chromatography, reaction with aminopyrazolone, and reaction showing bromide ions. The tests are used to verify the identity and ensure the compound meets purity standards of 99.0-101.0% before use as a pharmaceutical.
This document describes tests to analyze the purity of the pharmaceutical compound fenoterol hydrobromide. It provides specifications for 7 tests: appearance of solution, pH, related substances analysis by liquid chromatography, infrared absorption spectrophotometry, thin-layer chromatography, reaction with aminopyrazolone, and reaction showing bromide ions. The tests are used to verify the identity and ensure the compound meets purity standards of 99.0-101.0% before use as a pharmaceutical.
This document describes tests to analyze the purity of the pharmaceutical compound fenoterol hydrobromide. It provides specifications for 7 tests: appearance of solution, pH, related substances analysis by liquid chromatography, infrared absorption spectrophotometry, thin-layer chromatography, reaction with aminopyrazolone, and reaction showing bromide ions. The tests are used to verify the identity and ensure the compound meets purity standards of 99.0-101.0% before use as a pharmaceutical.
This document describes tests to analyze the purity of the pharmaceutical compound fenoterol hydrobromide. It provides specifications for 7 tests: appearance of solution, pH, related substances analysis by liquid chromatography, infrared absorption spectrophotometry, thin-layer chromatography, reaction with aminopyrazolone, and reaction showing bromide ions. The tests are used to verify the identity and ensure the compound meets purity standards of 99.0-101.0% before use as a pharmaceutical.
A. R-H : (4-chlorophenyl)(4-hydroxyphenyl)methanone,
B. 2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropanoic acid (fenobric acid),
C. (3RS)-3-[4-(4-chlorobenzoyl)phenoxy]butan-2-one,
D. methyl 2-[4-(4-chlorobenzoyl)phenoxy]-2methylpropanoate,
E. ethyl 2-[4-(4-chlorobenzoyl)phenoxy]-2methylpropanoate,
F. (4-chlorophenyl)[4-(1-methylethoxy)phenyl]methanone,
G. 1-methylethyl 2-[[2-[4-(4-chlorobenzoyl)phenoxy]-2methylpropanoyl]oxy]-2-methylpropanoate.
EUROPEAN PHARMACOPOEIA 8.0
Test solution. Dissolve 50.0 mg in dilute hydrochloric
acid R1 and dilute to 50.0 mL with the same acid. Dilute 5.0 mL of this solution to 50.0 mL with dilute hydrochloric acid R1. Spectral range : 230-350 nm. Absorption maximum : at 275 nm. Shoulder : at about 280 nm. Specific absorbance at the absorption maximum : 80 to 86. B. Infrared absorption spectrophotometry (2.2.24). Comparison : fenoterol hydrobromide CRS. C. Thin-layer chromatography (2.2.27). Test solution. Dissolve 10 mg of the substance to be examined in ethanol (96 per cent) R and dilute to 10 mL with the same solvent. Reference solution. Dissolve 10 mg of fenoterol hydrobromide CRS in ethanol (96 per cent) R and dilute to 10 mL with the same solvent. Plate : TLC silica gel G plate R. Mobile phase : concentrated ammonia R, water R, aldehyde-free methanol R (1.5:10:90 V/V/V). Application : 2 L. Development : over a path of 15 cm. Drying : in air. Detection : spray with a 10 g/L solution of potassium permanganate R. Results : the principal spot in the chromatogram obtained with the test solution is similar in position, colour and size to the principal spot in the chromatogram obtained with the reference solution. D. Dissolve about 10 mg in a 20 g/L solution of disodium tetraborate R and dilute to 50 mL with the same solution. Add 1 mL of a 10 g/L solution of aminopyrazolone R, 10 mL of a 2 g/L solution of potassium ferricyanide R and 10 mL of methylene chloride R. Shake and allow to separate. A reddish-brown colour develops in the lower layer. E. It gives reaction (a) of bromides (2.3.1).
TESTS Solution S. Dissolve 2.00 g in carbon dioxide-free water R and 01/2008:0901 dilute to 50.0 mL with the same solvent. corrected 7.1 Appearance of solution. Solution S is clear (2.2.1) and not more intensely coloured than reference solution Y7 (2.2.2, FENOTEROL HYDROBROMIDE Method II). pH (2.2.3): 4.2 to 5.2 for solution S. Fenoteroli hydrobromidum Related substances. Liquid chromatography (2.2.29). Prepare the solutions immediately before use. Test solution. Dissolve 24.0 mg of the substance to be examined in water R and dilute to 20.0 mL with the same solvent. Reference solution (a). Dissolve 24.0 mg of fenoterol hydrobromide CRS (containing impurity A) in water R and C17H22BrNO4 Mr 384.3 dilute to 20.0 mL with the same solvent. [1944-12-3] Reference solution (b). Dissolve the contents of a vial of fenoterol for peak identification CRS (containing impurities B DEFINITION and C) in 1.0 mL of water R. (1RS)-1-(3,5-Dihydroxyphenyl)-2-[[(1RS)-2-(4hydroxyphenyl)-1-methylethyl]amino]ethanol hydrobromide. Reference solution (c). Dilute 10.0 mL of the test solution to 50.0 mL with water R. Dilute 1.0 mL of this solution to Content : 99.0 per cent to 101.0 per cent (dried substance). 100.0 mL with water R. CHARACTERS Column : Appearance : white or almost white, crystalline powder. size : l = 0.15 m, = 4.6 mm ; Solubility : soluble in water and in ethanol (96 per cent). stationary phase : octadecylsilyl silica gel for chromatography R (5 m). IDENTIFICATION Mobile phase. Dissolve 24 g of anhydrous disodium hydrogen First identification : B, E. phosphate R in 1000 mL of water R. Mix 69 volumes of Second identification : A, C, D, E. this solution and 1 volume of a 9 g/L solution of potassium A. Ultraviolet and visible absorption spectrophotometry dihydrogen phosphate R, adjust to pH 8.5 with phosphoric (2.2.25). acid R and add 35 volumes of methanol R2.
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See the information section on general monographs (cover pages)
Fentanyl
EUROPEAN PHARMACOPOEIA 8.0
Flow rate : 1 mL/min.
Detection : spectrophotometer at 215 nm. Injection : 20 L. Run time : 3 times the retention time of fenoterol. 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 : resolution : minimum 3 between the peaks due to fenoterol and impurity A in the chromatogram obtained with reference solution (a) ; minimum 1.5 between the peaks due to impurities B and C in the chromatogram obtained with reference solution (b). Limits : correction factor : for the calculation of content, multiply the peak area of impurity B by 0.6 ; impurity A : maximum 4.0 per cent, calculated from the area of the corresponding peak in the chromatogram obtained with reference solution (a) and taking into account the declared content of impurity A in fenoterol hydrobromide CRS ; impurity C : not more than 1.5 times the area of the principal peak in the chromatogram obtained with reference solution (c) (0.3 per cent) ; impurity B : not more than the area of the principal peak in the chromatogram obtained with reference solution (c) (0.2 per cent) ; unspecified impurities : for each impurity, not more than 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (c) (0.10 per cent) ; sum of impurities other than A : not more than 1.5 times the area of the principal peak in the chromatogram obtained with reference solution (c) (0.3 per cent) ; disregard limit : 0.25 times the area of the principal peak in the chromatogram obtained with reference solution (c) (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.
B. 1-(3,5-dihydroxyphenyl)-2-[[(1RS)-2-(4-hydroxyphenyl)1-methylethyl]amino]ethanone,
C. (1RS)-1-(3,5-dihydroxyphenyl)-2-[[(1RS)-2-(4-hydroxy-3methylphenyl)-1-methylethyl]amino]ethanol. 01/2013:1210
FENTANYL Fentanylum
C22H28N2O [437-38-7]
Mr 336.5
DEFINITION N-Phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]propanamide. Content : 99.0 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance : white or almost white powder. Solubility : practically insoluble in water, freely soluble in ethanol (96 per cent) and in methanol. It shows polymorphism (5.9).
IDENTIFICATION Infrared absorption spectrophotometry (2.2.24). ASSAY Comparison : Ph. Eur. reference spectrum of fentanyl. Dissolve 0.600 g in 50 mL of water R and add 5 mL of dilute If the spectrum obtained in the solid state shows differences, nitric acid R, 25.0 mL of 0.1 M silver nitrate and 2 mL of ferric dissolve the substance to be examined in the minimum volume ammonium sulfate solution R2. Shake and titrate with 0.1 M of anhydrous ethanol R, evaporate to dryness at room ammonium thiocyanate until an orange colour is obtained. temperature under an air-stream and record a new spectrum Carry out a blank titration. using the residue. 1 mL of 0.1 M silver nitrate is equivalent to 38.43 mg TESTS of C17H22BrNO4. Related substances. Liquid chromatography (2.2.29). STORAGE Test solution. Dissolve 0.100 g of the substance to be examined Protected from light. in methanol R and dilute to 10.0 mL with the same solvent. Reference solution (a). Dissolve 10 mg of fentanyl for system IMPURITIES suitability CRS (containing impurities A, B, C, D and H) in Specified impurities : A, B, C. 1.0 mL of methanol R. Reference solution (b). 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. Column : size : l = 0.1 m, = 3.0 mm ; A. (1RS)-1-(3,5-dihydroxyphenyl)-2-[[(1SR)-2-(4 stationary phase : end-capped octadecylsilyl silica gel for hydroxyphenyl)-1-methylethyl]amino]ethanol, chromatography R (3 m). General Notices (1) apply to all monographs and other texts
