EUROPEAN PHARMACOPOEIA 11.

0 Dopamine hydrochloride

Sulfated ash (2.4.14) : maximum 0.1 per cent, determined on 01/2017:0664

1.0 g.
ASSAY
Liquid chromatography (2.2.29) as described in the test for
related substances with the following modification.
Injection : 20 μL of test solution (b) and reference solution (b). DOPAMINE HYDROCHLORIDE
Calculate the percentage content of C24H30ClNO3 taking into
account the assigned content of donepezil hydrochloride CRS. Dopamini hydrochloridum
IMPURITIES
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 C8H12ClNO2 Mr 189.6
by the general monograph Substances for pharmaceutical [62-31-7]
use (2034). It is therefore not necessary to identify these
DEFINITION
impurities for demonstration of compliance. See also 5.10.
Control of impurities in substances for pharmaceutical use) : 4-(2-Aminoethyl)benzene-1,2-diol hydrochloride.
A, B, C, D, E, F, G. Content : 99.0 per cent to 101.0 per cent (dried substance).
CHARACTERS
Appearance : white or almost white, crystalline powder.
Solubility : freely soluble in water, soluble in ethanol (96 per
cent), sparingly soluble in acetone and in methylene chloride.
A. (2RS)-5,6-dimethoxy-2-[(piperidin-4-yl)methyl]-2,3- IDENTIFICATION
dihydro-1H-inden-1-one,
First identification : B, E.
Second identification : A, C, D, E.
A. Ultraviolet and visible absorption spectrophotometry
(2.2.25).
Test solution. Dissolve 40.0 mg in 0.1 M hydrochloric acid
B. 5,6-dimethoxy-2,3-dihydro-1H-inden-1-one, and dilute to 100.0 mL with the same acid. Dilute 10.0 mL
of this solution to 100.0 mL with 0.1 M hydrochloric acid.
Spectral range : 230-350 nm.
Absorption maximum : at 280 nm.
Specific absorbance at the absorption maximum : 136 to 150.
B. Infrared absorption spectrophotometry (2.2.24).
C. (2R)-2-[(S)-(1-benzylpiperidin-4-yl)(hydroxy)methyl]-5,6-
dimethoxy-2,3-dihydro-1H-inden-1-one, Comparison : dopamine hydrochloride CRS.
C. Dissolve about 5 mg in a mixture of 5 mL of 1 M
hydrochloric acid and 5 mL of water R. Add 0.1 mL of
sodium nitrite solution R containing 100 g/L of ammonium
molybdate R. A yellow colour develops which becomes red
on the addition of strong sodium hydroxide solution R.
D. Dissolve about 2 mg in 2 mL of water R and add 0.2 mL
D. (2RS)-5,6-dimethoxy-2-[(pyridin-4-yl)methyl]-2,3-
of ferric chloride solution R2. A green colour develops
dihydro-1H-inden-1-one,
which changes to bluish-violet on the addition of 0.1 g of
hexamethylenetetramine R.
E. It gives reaction (a) of chlorides (2.3.1).
TESTS
Appearance of solution. The solution is clear (2.2.1) and
E. 1-benzyl-4-[[(2RS)-5,6-dimethoxy-1-oxo-2,3-dihydro-1H- not more intensely coloured than reference solution B6 or Y6
inden-2-yl]methyl]pyridin-1-ium, (2.2.2, Method II).
Dissolve 0.4 g in water R and dilute to 10 mL with the same
solvent.
Acidity or alkalinity. Dissolve 0.5 g in carbon dioxide-free
water R and dilute to 10 mL with the same solvent. Add
0.1 mL of methyl red solution R and 0.75 mL of 0.01 M sodium
hydroxide. The solution is yellow. Add 1.5 mL of 0.01 M
F. (2E)-2-[(1-benzylpiperidin-4-yl)methylidene]-5,6- hydrochloric acid. The solution is red.
dimethoxy-2,3-dihydro-1H-inden-1-one, Related substances. Liquid chromatography (2.2.29). Protect
the solutions from light.
Buffer solution. Dissolve 21 g of citric acid monohydrate R
in 200 mL of 1 M sodium hydroxide and dilute to 1000 mL
with water R. To 600 mL of this solution add 400 mL of 0.1 M
hydrochloric acid.
G. (2RS)-2-[(1-benzyl-1,2,3,4-tetrahydropyridin-4- Test solution. Dissolve 50 mg of the substance to be examined
yl)methyl]-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one. in mobile phase A and dilute to 25 mL with mobile phase A.

General Notices (1) apply to all monographs and other texts 2591
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Dopexamine dihydrochloride EUROPEAN PHARMACOPOEIA 11.0

Reference solution (a). Dilute 1.0 mL of the test solution to (2034). It is therefore not necessary to identify these impurities
100.0 mL with mobile phase A. Dilute 1.0 mL of this solution for demonstration of compliance. See also 5.10. Control of
to 10.0 mL with mobile phase A. impurities in substances for pharmaceutical use): A, B, C.
Reference solution (b). Dissolve 10 mg of 3-O-methyldopamine
hydrochloride R (impurity B) and 10 mg of 4-O-
methyldopamine hydrochloride R (impurity A) in mobile
phase A and dilute to 100 mL with mobile phase A. Dilute
6 mL of this solution to 25 mL with mobile phase A. A. 5-(2-aminoethyl)-2-methoxyphenol (4-O-
Column : methyldopamine),
– size : l = 0.15 m, Ø = 3.9 mm ;
– stationary phase : spherical end-capped octadecylsilyl silica
gel for chromatography R (4 μm).
Mobile phase :
– mobile phase A : dissolve 1.08 g of sodium octanesulfonate R B. 4-(2-aminoethyl)-2-methoxyphenol (3-O-
in 880 mL of the buffer solution and add 50 mL of methyldopamine),
methanol R and 70 mL of acetonitrile R ;
– mobile phase B : dissolve 1.08 g of sodium octanesulfonate R
in 700 mL of the buffer solution and add 100 mL of
methanol R and 200 mL of acetonitrile R ;
Time Mobile phase A Mobile phase B
C. 2-(3,4-dimethoxyphenyl)ethanamine.
(min) (per cent V/V) (per cent V/V)
0-5 90 10 01/2017:1748
5 - 20 90 → 40 10 → 60

20 - 25 40 60

Flow rate : 1.0 mL/min.

Detection : spectrophotometer at 280 nm. DOPEXAMINE DIHYDROCHLORIDE
Injection : 10 μL.
Retention time : dopamine = about 5 min. Dopexamini dihydrochloridum
System suitability : reference solution (b) :
– resolution : minimum 5.0 between the peaks due to
impurities B and A.
Limits :
– unspecificied 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) ;
C22H34Cl2N2O2 Mr 429.4
– total : not more than twice the area of the principal peak [86484-91-5]
in the chromatogram obtained with reference solution (a)
(0.2 per cent) ; DEFINITION
– disregard limit : 0.5 times the area of the principal peak in 4-[2-[[6-[(2-Phenylethyl)amino]hexyl]amino]ethyl]benzene-
the chromatogram obtained with reference solution (a) 1,2-diol dihydrochloride.
(0.05 per cent). Content : 98.5 per cent to 101.0 per cent (anhydrous substance).
Loss on drying (2.2.32) : maximum 0.5 per cent, determined
on 1.000 g by drying in an oven at 105 °C for 2 h. CHARACTERS
Appearance : white or almost white, crystalline powder.
Sulfated ash (2.4.14) : maximum 0.1 per cent, determined on
1.0 g. Solubility : soluble in water, sparingly soluble in ethanol
(96 per cent) and in methanol, practically insoluble in acetone.
ASSAY
IDENTIFICATION
In order to avoid overheating in the reaction medium, mix
thoroughly throughout the titration and stop the titration A. Infrared absorption spectrophotometry (2.2.24).
immediately after the end-point has been reached. Comparison : dopexamine dihydrochloride CRS.
Dissolve 0.150 g in 10 mL of anhydrous formic acid R. Add B. It gives reaction (a) of chlorides (2.3.1).
50 mL of acetic anhydride R. Titrate with 0.1 M perchloric
TESTS
acid, determining the end-point potentiometrically (2.2.20).
1 mL of 0.1 M perchloric acid is equivalent to 18.96 mg Appearance of solution. The solution is clear (2.2.1) and not
of C8H12ClNO2. more intensely coloured than reference solution BY7 (2.2.2,
Method II).
STORAGE Dissolve 0.10 g in 0.1 M hydrochloric acid and dilute to 10 mL
In an airtight container, under nitrogen, protected from light. with the same acid.
pH (2.2.3) : 3.7 to 5.7.
IMPURITIES
Dissolve 0.20 g in carbon dioxide-free water R and dilute to
Other detectable impurities (the following substances would, 20 mL with the same solvent.
if present at a sufficient level, be detected by one or other of
the tests in the monograph. They are limited by the general Related substances. Liquid chromatography (2.2.29).
acceptance criterion for other/unspecified impurities and/or Test solution. Dissolve 0.100 g of the substance to be examined
by the general monograph Substances for pharmaceutical use in mobile phase A and dilute to 10.0 mL with mobile phase A.

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