EUROPEAN PHARMACOPOEIA 10.

0 Paracetamol

System suitability : reference solution (b) :

– resolution : minimum 1.5 between the peaks due to
impurity A and papaverine.
Limits :
– correction factors : for the calculation of contents,
multiply the peak areas of the following impurities by
the corresponding correction factor : impurity A = 6.2 ; E. (1RS)-1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-
impurity C = 2.7 ; impurity D = 0.5 ; tetrahydroisoquinoline (tetrahydropapaverine),
– any impurity : not more than the area of the principal peak
in the chromatogram obtained with reference solution (a)
(0.1 per cent) ;
– total : not more than 5 times the area of the principal peak
in the chromatogram obtained with reference solution (a)
(0.5 per cent) ;
– disregard limit : 0.5 times the area of the principal peak in
the chromatogram obtained with reference solution (a) F. 2-(3,4-dimethoxyphenyl)-N-[2-(3,4-dimethoxyphenyl)-
(0.05 per cent). ethyl]acetamide.
Loss on drying (2.2.32): maximum 0.5 per cent, determined
on 1.000 g by drying in an oven at 105 °C. 04/2018:0049
Sulfated ash (2.4.14) : maximum 0.1 per cent, determined on
the residue from the test for loss on drying.
ASSAY
Dissolve 0.300 g in a mixture of 5.0 mL of 0.01 M hydrochloric PARACETAMOL
acid and 50 mL of alcohol R. Carry out a potentiometric
titration (2.2.20), using 0.1 M sodium hydroxide. Read the
volume added between the 2 points of inflexion. Paracetamolum
1 mL of 0.1 M sodium hydroxide is equivalent to 37.59 mg
of C20H22ClNO4.
IMPURITIES
C8H9NO2 Mr 151.2
[103-90-2]
DEFINITION
N-(4-Hydroxyphenyl)acetamide.
Content : 99.0 per cent to 101.0 per cent (dried substance).
CHARACTERS
Appearance : white or almost white, crystalline powder.
A. (3S)-6,7-dimethoxy-3-[(5R)-4-methoxy-6-methyl- Solubility : sparingly soluble in water, freely soluble in ethanol
5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinolin-5- (96 per cent), very slightly soluble in methylene chloride.
yl]isobenzofuran-1(3H)-one (noscapine),
IDENTIFICATION
First identification : B.
Second identification : A.
A. Melting point (2.2.14).
Determination A : determine the melting point of the
substance to be examined.
B. (RS)-(3,4-dimethoxyphenyl)(6,7-dimethoxyisoquinolin-1- Result A : 168 °C to 172 °C.
yl)methanol (papaverinol), Determination B : mix equal parts of the substance to be
examined and paracetamol CRS and determine the melting
point of the mixture.
Result B : the absolute difference between the melting point
of the mixture and the value obtained in determination A
is not greater than 2 °C.
B. Infrared absorption spectrophotometry (2.2.24).
Comparison : paracetamol CRS.
C. 1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-3,4-
dihydroisoquinoline (dihydropapaverine), TESTS
Related substances. Liquid chromatography (2.2.29).
Solvent mixture : methanol R, water R (15:85 V/V).
Test solution. Dissolve 50.0 mg of the substance to be
examined in the solvent mixture and dilute to 5.0 mL with the
solvent mixture.
Reference solution (a). Dilute 1.0 mL of the test solution to
D. (3,4-dimethoxyphenyl)(6,7-dimethoxyisoquinolin-1- 100.0 mL with the solvent mixture. Dilute 1.0 mL of this
yl)methanone (papaveraldine), solution to 20.0 mL with the solvent mixture.

General Notices (1) apply to all monographs and other texts 3481
Paracetamol EUROPEAN PHARMACOPOEIA 10.0

Reference solution (b). Prepare immediately before use. ASSAY

Dissolve 5.0 mg of paracetamol impurity K CRS and 5 mg of Dissolve 0.300 g in a mixture of 10 mL of water R and 30 mL
paracetamol CRS in the solvent mixture and dilute to 100.0 mL of dilute sulfuric acid R. Boil under a reflux condenser for 1 h,
with the solvent mixture. Dilute 1.0 mL of the solution to cool and dilute to 100.0 mL with water R. To 20.0 mL of the
100.0 mL with the solvent mixture. solution add 40 mL of water R, 40 g of ice, 15 mL of dilute
Reference solution (c). Dissolve 5.0 mg of paracetamol hydrochloric acid R and 0.1 mL of ferroin R. Titrate with 0.1 M
impurity J CRS in the solvent mixture and dilute to 250.0 mL cerium sulfate until a greenish-yellow colour is obtained.
with the solvent mixture. Dilute 1.0 mL of the solution to Carry out a blank titration.
200.0 mL with the solvent mixture. 1 mL of 0.1 M cerium sulfate is equivalent to 7.56 mg of
Precolumn : C8H9NO2.
– size : l = 0.005 m, Ø = 2.1 mm ;
STORAGE
– stationary phase : end-capped solid core octadecylsilyl silica
gel for chromatography R (2.7 μm). Protected from light.
Column : IMPURITIES
– size : l = 0.10 m, Ø = 2.1 mm ; Specified impurities : J, K.
– stationary phase : end-capped solid core octadecylsilyl silica
Other detectable impurities (the following substances would,
gel for chromatography R (2.7 μm) ;
if present at a sufficient level, be detected by one or other of
– temperature : 30 °C. the tests in the monograph. They are limited by the general
Mobile phase : acceptance criterion for other/unspecified impurities and/or
– mobile phase A : dissolve 1.7 g of potassium dihydrogen by the general monograph Substances for pharmaceutical
phosphate R and 1.8 g of dipotassium hydrogen phosphate R use (2034). It is therefore not necessary to identify these
in water for chromatography R and dilute to 1000 mL with impurities for demonstration of compliance. See also 5.10.
the same solvent ; Control of impurities in substances for pharmaceutical use) : A,
– mobile phase B : methanol R ; B, C, D, E, F, G, H, I, L, M, N.
Time Mobile phase A Mobile phase B
(min) (per cent V/V) (per cent V/V)
0-1 95 5

1 - 10 95 → 90 5 → 10
A. N-(2-hydroxyphenyl)acetamide,
10 - 20 90 10

20 - 40 90 → 66 10 → 34

40 - 50 66 34

Flow rate : 0.3 mL/min.

B. N-(4-hydroxyphenyl)propanamide,
Detection : spectrophotometer at 254 nm.
Injection : 5 μL.
Identification of impurities : use the chromatogram obtained
with reference solution (b) to identify the peak due to
impurity K ; use the chromatogram obtained with reference
solution (c) to identify the peak due to impurity J.
Relative retention with reference to paracetamol (retention C. N-(3-chloro-4-hydroxyphenyl)acetamide,
time = about 4 min) : impurity K = about 0.4 ; impurity J = about
10.1.
System suitability : reference solution (b) :
– resolution : minimum 5.0 between the peaks due to
impurity K and paracetamol.
Calculation of percentage contents : D. N-phenylacetamide,
– for impurity J, use the concentration of impurity J in
reference solution (c) ;
– for impurity K, use the concentration of impurity K in
reference solution (b);
– for impurities other than J and K, use the concentration of
paracetamol in reference solution (a). E. 1-(4-hydroxyphenyl)ethan-1-one,
Limits :
– impurity K : maximum 50 ppm ;
– impurity J : maximum 10 ppm ;
– unspecified impurities : for each impurity, maximum
0.05 per cent ; F. 4-nitrophenol,
– total : maximum 0.2 per cent ;
– reporting threshold : 0.03 per cent, except for impurities J
and K.
Loss on drying (2.2.32): maximum 0.5 per cent, determined
on 1.000 g by drying in an oven at 105 °C.
Sulfated ash (2.4.14) : maximum 0.1 per cent, determined on
1.0 g. G. [1-(4-hydroxyphenyl)ethylidene]hydroxylamine,

3482 See the information section on general monographs (cover pages)

EUROPEAN PHARMACOPOEIA 10.0 Paraffin, light liquid

Preparation : place about 2 mg on a sodium chloride plate,

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.
H. 4-acetamidophenyl acetate, B. Acidity or alkalinity (see Tests).
C. Melting point (2.2.16) : 50 °C to 61 °C.
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
I. 1-(2-hydroxyphenyl)ethan-1-one,
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
the indicator to red. To a further 10 mL of the aqueous layer
add 0.1 mL of methyl red solution R. The solution is yellow.
Not more than 0.5 mL of 0.01 M hydrochloric acid is required
to change the colour of the indicator to red.
J. N-(4-chlorophenyl)acetamide (chloroacetanilide),
Polycyclic aromatic hydrocarbons. Use reagents for
ultraviolet absorption spectrophotometry. Dissolve 0.50 g in
25 mL of heptane R and place in a 125 mL separating funnel
with unlubricated ground-glass parts (stopper, stopcock). Add
5.0 mL of dimethyl sulfoxide R. Shake vigorously for 1 min
K. 4-aminophenol, and allow to stand until 2 clear layers are formed. Transfer the
lower layer to a 2nd separating funnel, add 2 mL of heptane R
and shake the mixture vigorously. Allow to stand until 2 clear
layers are formed. Separate the lower layer and measure its
absorbance (2.2.25) between 265 nm and 420 nm using as
the compensation liquid the clear lower layer obtained by
vigorously shaking 5.0 mL of dimethyl sulfoxide R with 25 mL
L. N-[4-(4-acetamido-2-hydroxyphenoxy)phenyl]acetamide, of heptane R for 1 min. Prepare a 7.0 mg/L reference solution
of naphthalene R in dimethyl sulfoxide R and measure the
absorbance of this solution at the absorption maximum at
278 nm using dimethyl sulfoxide R as the compensation liquid.
At wavelengths from 265 nm to 420 nm, the absorbance of the
test solution is not greater than one-third that of the reference
M. 4,4′-azanediyldiphenol, solution at 278 nm.
Sulfates (2.4.13): maximum 150 ppm.
Introduce 2.0 g of the melted substance to be examined into a
50 mL ground-glass-stoppered separating funnel. Add 30 mL
of boiling distilled water R, shake vigorously for 1 min and
filter.
N. N,N′-[oxydi(4,1-phenylene)]diacetamide.
STORAGE
Protected from light.
01/2008:1034

07/2018:0240

PARAFFIN, HARD
Paraffinum solidum PARAFFIN, LIGHT LIQUID
DEFINITION Paraffinum perliquidum
A purified mixture of solid saturated hydrocarbons generally
obtained from petroleum. It may contain a suitable DEFINITION
antioxidant. Purified mixture of liquid saturated hydrocarbons obtained
from petroleum.
CHARACTERS
Appearance : colourless or white or almost white mass ; the CHARACTERS
melted substance is free from fluorescence in daylight. Appearance : colourless, transparent, oily liquid, free from
Solubility : practically insoluble in water, freely soluble in fluorescence in daylight.
methylene chloride, practically insoluble in ethanol (96 per Solubility : practically insoluble in water, slightly soluble in
cent). ethanol (96 per cent), miscible with hydrocarbons.
IDENTIFICATION IDENTIFICATION
First identification : A, C. First identification : A, C.
Second identification : B, C. Second identification : B, C.
A. Infrared absorption spectrophotometry (2.2.24). A. Infrared absorption spectrophotometry (2.2.24).
Comparison : hard paraffin CRS. Comparison : Ph. Eur. reference spectrum of liquid paraffin.

General Notices (1) apply to all monographs and other texts 3483