Phenylbutazone
Phenylbutazone
Phenylbutazone
0 Phenylbutazone
General Notices (1) apply to all monographs and other texts 2229
Phenylbutazone EUROPEAN PHARMACOPOEIA 5.0
sodium nitrite R. A yellow colour is produced. To 1 ml of System suitability : reference solution (b) :
the solution add a solution of 10 mg of β-naphthol R in — resolution : minimum 2.0 between the peaks due to
5 ml of sodium carbonate solution R. A brownish-red to phenylbutazone and to impurity B.
violet-red precipitate is formed.
Limits :
TESTS — correction factor : for the calculation of content, multiply
Solution S. Dissolve 1.0 g with shaking in 20 ml of dilute the peak area of impurity C by 0.55,
sodium hydroxide solution R and maintain the solution at — impurities A, B : for each impurity, not more than 2.5 times
25 °C for 3 h. the area of the principal peak in the chromatogram
Appearance of solution. Solution S is clear (2.2.1). obtained with reference solution (a) (0.25 per cent),
Acidity or alkalinity. Heat to boiling 1.0 g in 50 ml of — impurity C : not more than twice the area of the principal
water R, cool with shaking in a closed flask and filter. peak in the chromatogram obtained with reference
To 25 ml of the filtrate add 0.5 ml of phenolphthalein solution (a) (0.20 per cent),
solution R. The solution is colourless. Not more than 0.5 ml — any other impurity : not more than the area of the
of 0.01 M sodium hydroxide is required to change the colour principal peak in the chromatogram obtained with
of the indicator. Add 0.6 ml of 0.01 M hydrochloric acid and reference solution (a) (0.1 per cent),
0.1 ml of methyl red solution R ; the solution is red or orange. — total : not more than 5 times the area of the principal peak
Absorbance (2.2.25) : maximum 0.20 for solution S at in the chromatogram obtained with reference solution (a)
420 nm in a 4 cm cell. (0.5 per cent),
Related substances. Liquid chromatography (2.2.29). — disregard limit : 0.25 times the area of the principal peak
Prepare the solutions immediately before use. in the chromatogram obtained with reference solution (a)
(0.025 per cent) ; disregard any peak due to impurity E.
Test solution. Dissolve 100.0 mg of the substance to be
examined in acetonitrile R and dilute to 10.0 ml with the Impurity E. Liquid chromatography (2.2.29) as described
same solvent. in the test for related substances with the following
modifications.
Reference solution (a). Dilute 1.0 ml of the test solution to
100.0 ml with acetonitrile R. Dilute 1.0 ml to 10.0 ml with Detection : spectrophotometer at 280 nm.
acetonitrile R. Injection : test solution and reference solution (c).
Reference solution (b). Dissolve 5 mg of phenylbutazone System suitability : reference solution (c) :
impurity B CRS and 5 mg of 1,2-diphenylhydrazine R in
— signal-to-noise ratio : minimum 10 for the principal peak.
acetonitrile R, add 0.5 ml of the test solution and dilute
to 50 ml with acetonitrile R. Dilute 2.5 ml to 10 ml with Limit :
acetonitrile R. — impurity E : not more than the area of the principal peak
Reference solution (c). Dissolve 1.0 mg of benzidine R in in the chromatogram obtained with reference solution (c)
acetonitrile R and dilute to 100.0 ml with the same solvent. (5 ppm).
Dilute 1.0 ml to 100.0 ml with acetonitrile R. Dilute 5.0 ml Heavy metals (2.4.8) : maximum 20 ppm.
to 10.0 ml with acetonitrile R.
1.0 g complies with limit test C. Prepare the standard using
Column : 2 ml of lead standard solution (10 ppm Pb) R.
— size : l = 0.125 m, Ø = 4.0 mm, Loss on drying (2.2.32) : maximum 0.2 per cent, determined
— stationary phase: octadecylsilyl silica gel for on 1.000 g by drying in vacuo at 80 °C for 4 h.
chromatography R (5 µm), Sulphated ash (2.4.14) : maximum 0.1 per cent, determined
— temperature : 30 °C. on 1.0 g.
Mobile phase :
ASSAY
— mobile phase A : dissolve 1.36 g of sodium acetate R in
water R, adjust to pH 5.2 with a 52.5 g/l solution of citric Dissolve 0.250 g in 25 ml of acetone R and add 0.5 ml of
acid R and dilute to 1000 ml with water R, bromothymol blue solution R1. Titrate with 0.1 M sodium
hydroxide until a blue colour is obtained which persists for
— mobile phase B : acetonitrile R, 15 s. Carry out a blank titration.
Time Mobile phase A Mobile phase B 1 ml of 0.1 M sodium hydroxide is equivalent to 30.84 mg
(min) (per cent V/V) (per cent V/V) of C19H20N2O2.
0 - 10 70 30
STORAGE
10 - 20 70 → 40 30 → 60
Protected from light.
20 - 35 40 60
35 - 40 40 → 70 60 → 30
IMPURITIES
TESTS
Appearance of solution. Dissolve 1 g in 1 M hydrochloric
B. 4-butyl-4-hydroxy-1,2-diphenylpyrazolidine-3,5-dione, acid and dilute to 10 ml with the same acid. The solution is
clear (2.2.1) and not more intensely coloured than reference
C. C6H5-NH-NH-C6H5 : 1,2-diphenyldiazane, solution Y7 (2.2.2, Method II).
(1,2-diphenylhydrazine), Specific optical rotation (2.2.7). Dissolve 1.250 g in 1 M
hydrochloric acid and dilute to 25.0 ml with the same acid.
D. C6H5-N=N-C6H5 : 1,2-diphenyldiazene, The specific optical rotation is − 53 to − 57, calculated with
reference to the dried substance.
Absorbance. Dissolve 0.50 g in 0.1 M hydrochloric acid
and dilute to 200 ml with the same solvent. Measure the
absorbance (2.2.25) at 315 nm using 0.1 M hydrochloric
acid as the compensation liquid. The absorbance is not more
E. biphenyl-4,4′-diamine (benzidine). than 0.15 (0.4 per cent, calculated as impurity C).
Related substances. Examine by thin-layer chromatography
(2.2.27), using silica gel HF254 R as the coating substance.
Solvent mixture. Prepare a mixture of equal volumes of
01/2005:1035 methylene chloride R and methanolic hydrochloric acid
hydrochloric acid R diluted to 10 volumes with methanol R.
PHENYLEPHRINE Test solution. Dissolve 0.1 g of the substance to be examined
in the solvent mixture and dilute to 5 ml with the same
solvent mixture.
Phenylephrinum Reference solution (a). Dissolve 20 mg of
phenylephrine CRS in the solvent mixture and
dilute to 1 ml with the same solvent mixture.
Reference solution (b). Dilute 0.1 ml of the test solution to
20 ml with the solvent mixture.
Reference solution (c). Dilute 0.1 ml of the test solution to
50 ml with the solvent mixture.
C9H13NO2 Mr 167.2
Apply separately to the plate 10 µl of each solution and
DEFINITION develop over a path of 15 cm using a mixture of 0.5 volumes
of concentrated ammonia R, 25 volumes of methanol R
Phenylephrine contains not less than 99.0 per cent
and 70 volumes of methylene chloride R. Dry the plate in a
and not more than the equivalent of 100.5 per cent of
current of cold air. Examine in ultraviolet light at 254 nm.
(1R)-1-(3-hydroxyphenyl)-2-(methylamino)ethanol, calculated
Spray with a 1 g/l solution of fast red B salt R in a 50 g/l
with reference to the dried substance.
solution of sodium carbonate R and examine in daylight.
Any spot in the chromatogram obtained with the test
CHARACTERS
solution, apart from the principal spot, is not more intense
A white or almost white, crystalline powder, slightly soluble than the spot in the chromatogram obtained with reference
in water, sparingly soluble in methanol, slightly soluble in solution (b) (0.5 per cent) and at most two such spots are
alcohol. It dissolves in dilute mineral acids and in dilute more intense than the spot in the chromatogram obtained
solutions of alkali hydroxides. with reference solution (c) (0.2 per cent).
It melts at about 174 °C. Loss on drying (2.2.32). Not more than 0.5 per cent,
determined on 1.000 g by drying in an oven at 100 °C to
IDENTIFICATION 105 °C.
First identification : A, B. Sulphated ash (2.4.14). Not more than 0.1 per cent,
Second identification : A, C, D. determined on 1.0 g.
A. It complies with the test for specific optical rotation (see ASSAY
Tests).
Dissolve 0.150 g in 60 ml of anhydrous acetic acid R.
B. Examine by infrared absorption spectrophotometry Titrate with 0.1 M perchloric acid determining the end-point
(2.2.24), comparing with the spectrum obtained with potentiometrically (2.2.20).
phenylephrine CRS.
1 ml of 0.1 M perchloric acid is equivalent to 16.72 mg of
C. Examine the chromatograms obtained in the test
C9H13NO2.
for related substances. The principal spot in the
chromatogram obtained with the test solution is similar
in position, colour and size to the principal spot in the STORAGE
chromatogram obtained with reference solution (a). Store in an airtight container, protected from light.
General Notices (1) apply to all monographs and other texts 2231