Paracetamol EUROPEAN PHARMACOPOEIA 11.

04/2022:0049 – temperature : 30 °C.

Mobile phase :
– mobile phase A : dissolve 1.7 g of potassium dihydrogen
phosphate R and 1.8 g of dipotassium hydrogen phosphate R
in water for chromatography R and dilute to 1000 mL with
PARACETAMOL the same solvent ;
– mobile phase B : methanol R ;
Paracetamolum Time Mobile phase A Mobile phase B
(min) (per cent V/V) (per cent V/V)
0 - 1.5 95 5

1.5 - 14.4 95 → 90 5 → 10

14.4 - 28.8 90 10
C8H9NO2 Mr 151.2
[103-90-2] 28.8 - 57.6 90 → 66 10 → 34

57.6 - 60 66 34
DEFINITION
N-(4-Hydroxyphenyl)acetamide. Flow rate : 1.5 mL/min.
Content : 99.0 per cent to 101.0 per cent (dried substance). Detection : spectrophotometer at 254 nm.
Autosampler : set at 5 °C.
CHARACTERS
Injection : 50 μL of the test solution and reference solutions (a),
Appearance : white or almost white, crystalline powder. (b), (d) and (e).
Solubility : sparingly soluble in water, freely soluble in ethanol Identification of impurities: use the chromatogram obtained
(96 per cent), very slightly soluble in methylene chloride. with reference solution (b) to identify the peak due to
IDENTIFICATION impurity J ; use the chromatogram obtained with reference
solution (d) to identify the peak due to impurity K.
First identification : B.
Relative retention with reference to paracetamol
Second identification : A. (retention time = about 4 min) : impurity K = about 0.4 ;
A. Melting point (2.2.14). impurity J = about 10.1.
Determination A : determine the melting point of the System suitability : reference solution (e):
substance to be examined. – resolution : minimum 5.0 between the peaks due to
Result A : 168 °C to 172 °C. impurity K and paracetamol.
Determination B : mix equal parts of the substance to be Calculation of contents :
examined and paracetamol CRS and determine the melting – for impurity J, use the concentration of impurity J in
point of the mixture. reference solution (b);
Result B : the absolute difference between the melting point – for impurity K, use the concentration of impurity K in
of the mixture and the value obtained in determination A reference solution (d) ;
is not greater than 2 °C. – for impurities other than J and K, use the concentration of
B. Infrared absorption spectrophotometry (2.2.24). paracetamol in reference solution (a).
Comparison : paracetamol CRS. Limits :
– impurity K : maximum 50 ppm ;
TESTS
– impurity J : maximum 10 ppm ;
Related substances. Liquid chromatography (2.2.29).
– unspecified impurities : for each impurity, maximum
Solvent mixture : methanol R, water R (15:85 V/V). 0.05 per cent ;
Test solution. Dissolve 50.0 mg of the substance to be – total : maximum 0.2 per cent ;
examined in 0.75 mL of methanol R and dilute to 5.0 mL with – reporting threshold : 0.03 per cent, except for impurities J
water R. and K.
Reference solution (a). Dilute 1.0 mL of the test solution to
100.0 mL with the solvent mixture. Dilute 1.0 mL of this Loss on drying (2.2.32) : maximum 0.5 per cent, determined
solution to 20.0 mL with the solvent mixture. on 1.000 g by drying in an oven at 105 °C.
Reference solution (b). Dissolve 5.0 mg of paracetamol Sulfated ash (2.4.14): maximum 0.1 per cent, determined on
impurity J CRS in 25 mL of methanol R and dilute to 250.0 mL 1.0 g.
with the solvent mixture. Dilute 1.0 mL of the solution to ASSAY
200.0 mL with the solvent mixture.
Dissolve 0.300 g in a mixture of 10 mL of water R and 30 mL
Reference solution (c). Dissolve 5.0 mg of paracetamol of dilute sulfuric acid R. Boil under a reflux condenser for 1 h,
impurity K CRS in the solvent mixture and dilute to 100.0 mL cool and dilute to 100.0 mL with water R. To 20.0 mL of the
with the solvent mixture. Dilute 1.0 mL of the solution to solution add 40 mL of water R, 40 g of ice, 15 mL of dilute
10.0 mL with the solvent mixture. hydrochloric acid R and 0.1 mL of ferroin R. Titrate with 0.1 M
Reference solution (d). Dilute 1.0 mL of reference solution (c) cerium sulfate until a greenish-yellow colour is obtained.
to 10.0 mL with the solvent mixture. Carry out a blank titration.
Reference solution (e). Mix 1 mL of reference solution (a) and 1 mL of 0.1 M cerium sulfate is equivalent to 7.56 mg of
1 mL of reference solution (c) and dilute to 10 mL with the C8H9NO2.
solvent mixture.
STORAGE
Column :
Protected from light.
– size : l = 0.15 m, Ø = 4.6 mm ;
– stationary phase : end-capped solid core octadecylsilyl silica IMPURITIES
gel for chromatography R (5 μm) ; Specified impurities : J, K.

3634 See the information section on general monographs (cover pages)

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EUROPEAN PHARMACOPOEIA 11.0 Paraffin, hard

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
by the general monograph Substances for pharmaceutical K. 4-aminophenol,
use (2034). It is therefore not necessary to identify these
impurities for demonstration of compliance. See also 5.10.
Control of impurities in substances for pharmaceutical use): A,
B, C, D, E, F, G, H, I, L, M, N, O.

L. N-[4-(4-acetamido-2-hydroxyphenoxy)phenyl]acetamide,

A. N-(2-hydroxyphenyl)acetamide,

M. 4,4′-azanediyldiphenol,

B. N-(4-hydroxyphenyl)propanamide,

N. N,N′-[oxydi(4,1-phenylene)]diacetamide,

C. N-(3-chloro-4-hydroxyphenyl)acetamide,
O. N-[4-(5-acetamido-2-hydroxyphenoxy)phenyl]acetamide.

01/2008:1034

D. N-phenylacetamide,

PARAFFIN, HARD
Paraffinum solidum
E. 1-(4-hydroxyphenyl)ethan-1-one,
DEFINITION
A purified mixture of solid saturated hydrocarbons generally
obtained from petroleum. It may contain a suitable
antioxidant.
F. 4-nitrophenol, CHARACTERS
Appearance : colourless or white or almost white mass ; the
melted substance is free from fluorescence in daylight.
Solubility : practically insoluble in water, freely soluble in
methylene chloride, practically insoluble in ethanol (96 per
cent).
IDENTIFICATION
G. [1-(4-hydroxyphenyl)ethylidene]hydroxylamine,
First identification : A, C.
Second identification : B, C.
A. Infrared absorption spectrophotometry (2.2.24).
Comparison : hard paraffin CRS.
Preparation : place about 2 mg on a sodium chloride plate,
H. 4-acetamidophenyl acetate, heat in an oven at 100 °C for 10 min, spread the melted
substance with another sodium chloride plate and remove
one of the plates.
B. Acidity or alkalinity (see Tests).
C. Melting point (2.2.16) : 50 °C to 61 °C.

I. 1-(2-hydroxyphenyl)ethan-1-one, TESTS
Acidity or alkalinity. To 15 g add 30 mL of boiling water R
and shake vigorously for 1 min. Allow to cool and to separate.
To 10 mL of the aqueous layer add 0.1 mL of phenolphthalein
solution R. The solution is colourless. Not more than 1.0 mL
of 0.01 M sodium hydroxide is required to change the colour of
J. N-(4-chlorophenyl)acetamide (chloroacetanilide), the indicator to red. To a further 10 mL of the aqueous layer

General Notices (1) apply to all monographs and other texts 3635
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