EUROPEAN PHARMACOPOEIA 8.

0 Diclofenac potassium

Limits :
– correction factors : for the calculation of contents,
multiply the peak areas of the following impurities by
the corresponding correction factor : impurity D = 1.9 ;
impurity H = 1.4, E. R = NH2 : (RS)-(4-amino-2,6-dichlorophenyl)(4-
– impurity D : not more than 0.4 times the area of the chlorophenyl)acetonitrile,
principal peak in the chromatogram obtained with H. R = H : (RS)-(4-chlorophenyl)(2,6-dichlorophenyl)-
reference solution (b) (0.1 per cent), acetonitrile,
– any other impurity : not more than the area of the principal
peak in the chromatogram obtained with reference
solution (b) (0.25 per cent),
– total : not more than 4 times the area of the principal peak
in the chromatogram obtained with reference solution (b)
(1.0 per cent),
– disregard limit : 0.2 times the area of the principal peak in
the chromatogram obtained with reference solution (b)
(0.05 per cent).
Loss on drying (2.2.32): maximum 0.5 per cent, determined I. N,2-bis[3,5-dichloro-4-[(4-chlorophenyl)cyanomethyl]-
on 1.000 g by drying in an oven at 105 °C for 4 h. phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-
carboxamide.
Sulfated ash (2.4.14) : maximum 0.1 per cent, determined on
1.0 g.
01/2008:1508
ASSAY
Dissolve 0.150 g in 75 mL of dimethylformamide R. DICLOFENAC POTASSIUM
Carry out a potentiometric titration (2.2.20), using 0.1 M
tetrabutylammonium hydroxide. Read the volume added at Diclofenacum kalicum
the second inflexion point. Carry out a blank titration.
1 mL of 0.1 M tetrabutylammonium hydroxide is equivalent
to 20.38 mg of C17H9Cl3N4O2.
STORAGE
Protected from light.
IMPURITIES
Specified impurities : A, B, C, D, E, F, G, H, I. C14H10Cl2KNO2 Mr 334.2
[15307-81-0]
DEFINITION
Potassium [2-[(2,6-dichlorophenyl)amino]phenyl]acetate.
Content : 99.0 per cent to 101.0 per cent (dried substance).
CHARACTERS
Appearance : white or slightly yellowish, slightly hygroscopic,
crystalline powder.
A. R = Cl, R′ = CO2H : 2-[3,5-dichloro-4-[(RS)-(4- Solubility : sparingly soluble in water, freely soluble in
chlorophenyl)cyanomethyl]phenyl]-3,5-dioxo-2,3,4,5- methanol, soluble in ethanol (96 per cent), slightly soluble
tetrahydro-1,2,4-triazine-6-carboxylic acid, in acetone.
B. R = OH, R′ = H : (RS)-[2,6-dichloro-4-(3,5-dioxo- IDENTIFICATION
4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl](4-
hydroxyphenyl)acetonitrile, First identification : A, D.
Second identification : B, C, D.
C. R = Cl, R′ = CONH2 : 2-[3,5-dichloro-4-[(RS)-(4- A. Infrared absorption spectrophotometry (2.2.24).
chlorophenyl)cyanomethyl]phenyl]-3,5-dioxo-2,3,4,5- Preparation : discs.
tetrahydro-1,2,4-triazine-6-carboxamide,
Comparison : diclofenac potassium CRS.
G. R = Cl, R′ = CO-O-[CH2]3-CH3 : butyl 2-[3,5-dichloro-4- B. Thin-layer chromatography (2.2.27).
[(RS)-(4-chlorophenyl)cyanomethyl]phenyl]-3,5-dioxo- Test solution. Dissolve 25 mg of the substance to be
2,3,4,5-tetrahydro-1,2,4-triazine-6-carboxylate, examined in methanol R and dilute to 5 mL with the same
solvent.
Reference solution (a). Dissolve 25 mg of diclofenac
potassium CRS in methanol R and dilute to 5 mL with the
same solvent.
Reference solution (b). Dissolve 10 mg of indometacin R
in reference solution (a) and dilute to 2 mL with the same
solution.
D. X = O : 2-[3,5-dichloro-4-(4-chlorobenzoyl)phenyl]-1,2,4- Plate : TLC silica gel GF254 plate R.
triazine-3,5(2H,4H)-dione,
Mobile phase : concentrated ammonia R, methanol R, ethyl
F. X = H2 : 2-[3,5-dichloro-4-(4-chlorobenzyl)phenyl]-1,2,4- acetate R ([Link] V/V/V).
triazine-3,5(2H,4H)-dione, Application : 5 μL.

General Notices (1) apply to all monographs and other texts 2035
Diclofenac sodium EUROPEAN PHARMACOPOEIA 8.0

Development : over a path of 10 cm. Heavy metals (2.4.8): maximum 10 ppm.

Drying : in air. 2.0 g complies with test C. Use a quartz crucible. Prepare
Detection : examine in ultraviolet light at 254 nm. the reference solution using 2 mL of lead standard solution
(10 ppm Pb) R.
System suitability : reference solution (b):
Loss on drying (2.2.32) : maximum 0.5 per cent, determined
– the chromatogram shows 2 clearly separated spots. on 1.000 g by drying in an oven at 105 °C for 3 h.
Results : the principal spot in the chromatogram obtained
with the test solution is similar in position and size to ASSAY
the principal spot in the chromatogram obtained with Dissolve 0.250 g in 30 mL of anhydrous acetic acid R. Titrate
reference solution (a). with 0.1 M perchloric acid, determining the end-point
C. Dissolve about 10 mg in 10 mL of ethanol (96 per cent) R. potentiometrically (2.2.20).
To 1 mL of this solution add 0.2 mL of a mixture, prepared 1 mL of 0.1 M perchloric acid is equivalent to 33.42 mg
immediately before use, of equal volumes of a 6 g/L solution of C14H10Cl2KNO2.
of potassium ferricyanide R and a 9 g/L solution of ferric
chloride R. Allow to stand protected from light for 5 min. STORAGE
Add 3 mL of a 10 g/L solution of hydrochloric acid R. Allow In an airtight container, protected from light.
to stand protected from light for 15 min. A blue colour
develops and a precipitate is formed. IMPURITIES
D. Suspend 0.5 g in 10 mL of water R. Stir and add water R Specified impurities : A, B, C, D, E.
until the substance is dissolved. Add 2 mL of hydrochloric
acid R1, stir for 1 h and filter with the aid of vacuum.
Neutralise with sodium hydroxide solution R. The solution
gives reaction (b) of potassium (2.3.1).
TESTS
Appearance of solution. The solution is clear (2.2.1) and its
absorbance (2.2.25) at 440 nm is not greater than 0.05. A. 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indol-2-one,
Dissolve 1.25 g in methanol R and dilute to 25.0 mL with the
same solvent.
Related substances. Liquid chromatography (2.2.29).
Test solution. Dissolve 50.0 mg of the substance to be
examined in methanol R and dilute to 50.0 mL with the same
solvent.
Reference solution (a). Dilute 2.0 mL of the test solution to
100.0 mL with methanol R. Dilute 1.0 mL of this solution to B. R1 = CHO, R2 = Cl : 2-[(2,6-dichlorophenyl)amino]-
10.0 mL with methanol R. benzaldehyde,
Reference solution (b). Dilute 1.0 mL of the test solution to C. R1 = CH2OH, R2 = Cl : [2-[(2,6-dichlorophenyl)amino]-
200.0 mL with methanol R. In 1.0 mL of this solution dissolve phenyl]methanol,
the contents of a vial of diclofenac impurity A CRS. D. R1 = CH2-CO2H, R2 = Br : 2-[2-[(2-bromo-6-
Column : chlorophenyl)amino]phenyl]acetic acid,
– size : l = 0.25 m, Ø = 4.6 mm ;
– stationary phase : end-capped octylsilyl silica gel for
chromatography R (5 μm).
Mobile phase : mix 34 volumes of a solution containing E. 1,3-dihydro-2H-indol-2-one.
0.5 g/L of phosphoric acid R and 0.8 g/L of sodium dihydrogen
phosphate R, adjusted to pH 2.5 with phosphoric acid R, and
66 volumes of methanol R. 01/2008:1002
Flow rate : 1 mL/min.
DICLOFENAC SODIUM
Detection : spectrophotometer at 254 nm.
Injection : 20 μL. Diclofenacum natricum
Run time : 1.5 times the retention time of diclofenac.
Retention time : impurity A = about 12 min ; diclofenac = about
25 min.
System suitability : reference solution (b):
– resolution : minimum 6.5 between the peaks due to
impurity A and diclofenac.
Limits:
C14H10Cl2NNaO2 Mr 318.1
– impurities A, B, C, D, E : for each impurity, not more [15307-79-6]
than the area of the principal peak in the chromatogram
obtained with reference solution (a) (0.2 per cent) ; DEFINITION
– total : not more than 2.5 times the area of the principal peak Sodium 2-[(2,6-dichlorophenyl)amino]phenyl]acetate.
in the chromatogram obtained with reference solution (a) Content : 99.0 per cent to 101.0 per cent (dried substance).
(0.5 per cent) ;
– disregard limit : 0.25 times the area of the principal peak CHARACTERS
in the chromatogram obtained with reference solution (a) Appearance : white or slightly yellowish, slightly hygroscopic,
(0.05 per cent). crystalline powder.

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