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Fenoterol hydrobromide

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

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