EUROPEAN PHARMACOPOEIA 10.

0 Carvedilol

01/2017:1745 Flow rate: 1.0 mL/min.

Detection : spectrophotometer at 240 nm.
Injection : 20 µL.
Run time: 6 times the retention time of carvedilol.
CARVEDILOL Identification of impurities : use the chromatogram
supplied with carvedilol for system suitability CRS and the
chromatogram obtained with reference solution (c) to identify
Carvedilolum the peaks due to impurities A and D; use the chromatogram
obtained with reference solution (b) to identify the peak due
to impurity C.
Relative retention with reference to carvedilol (retention
time = about 4 min) : impurity A = about 0.5;
impurity C = about 2.9; impurity D = about 3.8.
System suitability :
C24H26N2O4 Mr 406.5 – resolution : minimum 3.5 between the peaks due to
[72956-09-3] impurity A and carvedilol in the chromatogram obtained
with reference solution (c) ;
DEFINITION – signal-to-noise ratio: minimum 10 for the peak due to
(2RS)-1-(9H-Carbazol-4-yloxy)-3-[[2-(2-methoxyphenoxy)- impurity C in the chromatogram obtained with reference
ethyl]amino]propan-2-ol. solution (b).
Content : 99.0 per cent to 101.0 per cent (dried substance). Limits:
– correction factor : for the calculation of content, multiply
CHARACTERS the peak area of impurity A by 2.0;
Appearance : white or almost white, crystalline powder. – impurity A : not more than twice the area of the principal
Solubility : practically insoluble in water, sparingly soluble in peak in the chromatogram obtained with reference
methylene chloride, slightly soluble in ethanol (96 per cent). solution (a) (0.2 per cent) ;
It is practically insoluble in dilute acids. – impurity D : not more than 1.5 times the area of the
It shows polymorphism (5.9). principal peak in the chromatogram obtained with
reference solution (a) (0.15 per cent) ;
IDENTIFICATION – impurity C : not more than the area of the corresponding
Infrared absorption spectrophotometry (2.2.24). peak in the chromatogram obtained with reference
solution (b) (0.02 per cent);
Comparison : carvedilol CRS.
– unspecified impurities : for each impurity, not more than the
If the spectra obtained show differences, dissolve the substance area of the principal peak in the chromatogram obtained
to be examined and the reference substance separately in with reference solution (a) (0.10 per cent) ;
2-propanol R, evaporate to dryness and record new spectra
using the residues. – sum of impurities other than C : not more than 5 times the
area of the principal peak in the chromatogram obtained
TESTS with reference solution (a) (0.5 per cent) ;
Related substances. Liquid chromatography (2.2.29). – disregard limit : 0.5 times the area of the principal peak in
the chromatogram obtained with reference solution (a)
Test solution. Dissolve 25 mg of the substance to be examined (0.05 per cent).
in the mobile phase and dilute to 25.0 mL with the mobile
phase. Loss on drying (2.2.32): maximum 0.5 per cent, determined
on 1.000 g by drying in an oven at 105 °C.
Reference solution (a). Dilute 1.0 mL of the test solution to
100.0 mL with the mobile phase. Dilute 1.0 mL of this solution Sulfated ash (2.4.14) : maximum 0.1 per cent, determined on
to 10.0 mL with the mobile phase. 1.0 g.
Reference solution (b). Dissolve 5 mg of carvedilol
ASSAY
impurity C CRS in 5.0 mL of the mobile phase and dilute to
100.0 mL with the mobile phase. Dilute 4.0 mL of the solution Dissolve 0.350 g in 60 mL of anhydrous acetic acid R. Titrate
to 100.0 mL with the mobile phase. Dilute 1.0 mL of this with 0.1 M perchloric acid, determining the end-point
solution to 10.0 mL with the mobile phase. potentiometrically (2.2.20).
Reference solution (c). Dissolve 5 mg of carvedilol for system 1 mL of 0.1 M perchloric acid is equivalent to 40.65 mg of
suitability CRS (containing impurities A and D) in the mobile C24H26N2O4.
phase and dilute to 50.0 mL with the mobile phase.
Column : IMPURITIES
– size: l = 0.150 m, Ø = 4.6 mm ; Specified impurities: A, C, D.
– stationary phase : end-capped octylsilyl silica gel for Other detectable impurities (the following substances would,
chromatography R (5 µm) ; if present at a sufficient level, be detected by one or other of
the tests in the monograph. They are limited by the general
– temperature : 55 °C. acceptance criterion for other/unspecified impurities and/or
Mobile phase : dissolve 1.77 g of potassium dihydrogen by the general monograph Substances for pharmaceutical
phosphate R in water R and dilute to 650 mL with the same use (2034). It is therefore not necessary to identify these
solvent; adjust to pH 2.0 with phosphoric acid R and add impurities for demonstration of compliance. See also 5.10.
350 mL of acetonitrile R. Control of impurities in substances for pharmaceutical use) : B.

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General Notices (1) apply to all monographs and other texts 2101
Castor oil, hydrogenated EUROPEAN PHARMACOPOEIA 10.0

IDENTIFICATION
A. Melting point (2.2.14) : 83 °C to 88 °C.
B. Hydroxyl value (see Tests).
C. Composition of fatty acids (see Tests).
TESTS
Acid value (2.5.1) : maximum 4.0, determined on 10.0 g
dissolved in 75 mL of hot ethanol (96 per cent) R.
A. 1-[[9-[2-hydroxy-3-[[2-(2-methoxyphenoxy)ethyl]amino]- Hydroxyl value (2.5.3, Method A) : 145 to 165, determined on
propyl]-9H-carbazol-4-yl]oxy]-3-[[2-(2- a warm solution.
methoxyphenoxy)ethyl]amino]propan-2-ol, Iodine value (2.5.4, Method A) : maximum 5.0.
Alkaline impurities. Dissolve 1.0 g with gentle heating in
a mixture of 1.5 mL of ethanol (96 per cent) R and 3 mL of
toluene R. Add 0.05 mL of a 0.4 g/L solution of bromophenol
blue R in ethanol (96 per cent) R. Not more than 0.2 mL of
0.01 M hydrochloric acid is required to change the colour of
the indicator to yellow.
Composition of fatty acids. Gas chromatography (2.4.22,
Method A) with the following modifications. Use the mixture
of calibrating substances in Table 2.4.22.-3.
Test solution. Introduce 75 mg of the substance to be examined
B. 1,1′-[[2-(2-methoxyphenoxy)ethyl]nitrilo]bis[3-(9H- into a 10 mL centrifuge tube with a screw cap. Dissolve in
carbazol-4-yloxy)propan-2-ol], 2 mL of 1,1-dimethylethyl methyl ether R1 by shaking and heat
gently (50-60 °C). Add, when still warm, 1 mL of a 12 g/L
solution of sodium R in anhydrous methanol R, prepared with
the necessary precautions, and mix vigorously for at least
5 min. Add 5 mL of distilled water R and mix vigorously for
about 30 s. Centrifuge for 15 min at 1500 g. Use the upper
layer.
Reference solution. Dissolve 50 mg of methyl
12-hydroxystearate CRS and 50 mg of methyl stearate CRS in
10.0 mL of 1,1-dimethylethyl methyl ether R1.
C. (2RS)-1-[benzyl[2-(2-methoxyphenoxy)ethyl]amino]-3- Column :
(9H-carbazol-4-yloxy)propan-2-ol, – material: fused silica ;
– size: l = 30 m; Ø = 0.25 mm ;
– stationary phase : macrogol 20 000 R (film thickness
0.25 µm).
Carrier gas : helium for chromatography R.
Flow rate: 0.9 mL/min.
Split ratio : 1:100.
Temperature :
Time Temperature
(min) (°C)
D. 1-(9H-carbazol-4-yloxy)-3-[4-[2-hydroxy-3-[[2-(2- Column 0 - 55 215
methoxyphenoxy)ethyl]amino]propoxy]-9H-carbazol-9-
yl]propan-2-ol. Injection port 250
Detector 250

01/2020:1497 Detection : flame ionisation.

Injection : 1 µL.
System suitability :
– symmetry factor : 0.7 to 1.5 for the peak due to methyl
stearate in the chromatogram obtained with the test
CASTOR OIL, HYDROGENATED solution.
Calculate the fraction of each fatty acid using the following
Ricini oleum hydrogenatum expression :
DEFINITION Ax , s , c / å Ax ,s , c ´ 100 per cent m / m
Fatty oil obtained by hydrogenation of Virgin castor oil (0051).
It consists mainly of the triglyceride of 12-hydroxystearic Ax,s,c = corrected peak area of the fatty acid in the test
((12Ξ)-12-hydroxyoctadecanoic) acid. solution :

CHARACTERS A x , s , c = Ax , s ´ R c
Appearance : fine, almost white or pale yellow powder or Rc = relative correction factor for the peak due to methyl
almost white or pale yellow masses or flakes. 12-hydroxystearate :
Solubility : practically insoluble in water, slightly soluble in
methylene chloride, very slightly soluble in anhydrous ethanol, m1, r ´ A 2, r
Rc =
practically insoluble in light petroleum. A1, r ´ m 2, r

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2102 See the information section on general monographs (cover pages)