Pyrantel embonate EUROPEAN PHARMACOPOEIA 10.

Reference solution (a). Dissolve 10 mg of pyrantel

impurity A CRS in the solvent mixture, add 2.5 mL of test
solution (b) and dilute to 50 mL with the solvent mixture.
Dilute 2 mL of this solution to 100 mL with the solvent
mixture.
B. 6-methoxy-8-nitroquinoline, Reference solution (b). Dilute 1.0 mL of test solution (b) to
200.0 mL with the mobile phase.
Reference solution (c). Dissolve 8.0 mg of pyrantel
impurity D CRS in acetonitrile R and dilute to 10.0 mL with
the same solvent. Dilute 1.0 mL of the solution to 100.0 mL
with acetonitrile R.
C. 6-methoxyquinolin-8-amine, Reference solution (d). Dissolve 8.0 mg of pyrantel
impurity C CRS in acetonitrile R and dilute to 10.0 mL with
the same solvent. Dilute 1.0 mL of the solution to 100.0 mL
with acetonitrile R.
Column :
– size : l = 0.25 m, Ø = 4.6 mm ;
– stationary phase : silica gel for chromatography R (5 μm) ;
– temperature : 30 °C.
Mobile phase : solvent mixture, acetonitrile for
D. 2-[(4RS)-4-[(6-methoxyquinolin-8-yl)amino]pentyl]-1H- chromatography R (72:928 V/V).
isoindole-1,3(2H)-dione. Flow rate : 1 mL/min.
Detection : spectrophotometer at 288 nm and, for impurity D,
at 238 nm.
04/2020:1680
Injection : 20 μL of test solution (b) and reference solutions (a),
(b) and (d) ; for impurity D, 50 μL of test solution (a) and
reference solution (c).
Run time : 4 times the retention time of pyrantel.
PYRANTEL EMBONATE Identification of impurities: use the chromatogram obtained
with reference solution (d) to identify the peak due to
impurity C ; use the chromatogram obtained with reference
Pyranteli embonas solution (c) to identify the peak due to impurity D.
Relative retention with reference to pyrantel (retention
time = about 11 min) : impurity C = about 0.3 ; embonic
acid = about 0.5 ; impurity A = about 1.3 ; impurity D = about
2.2.
System suitability : reference solution (a) :
– resolution : minimum 4.0 between the peaks due to pyrantel
and impurity A.
C34H30N2O6S Mr 594.7 Calculation of percentage contents :
[22204-24-6] – for impurity D, use the concentration of impurity D in
DEFINITION reference solution (c);
– for impurity C, use the concentration of impurity C in
1-Methyl-2-[(E)-2-(thiophen-2-yl)eth-1-en-1-yl]-1,4,5,6- reference solution (d);
tetrahydropyrimidine hydrogen 4,4′-methylenebis(3-
hydroxynaphthalene-2-carboxylate). – for impurities other than C and D, use the concentration of
pyrantel embonate in reference solution (b).
Content : 98.0 per cent to 102.0 per cent (dried substance).
Limits :
CHARACTERS – impurity D : maximum 0.2 per cent ;
Appearance : pale yellow or yellow powder. – impurity C : maximum 0.10 per cent ;
Solubility : practically insoluble in water, soluble in dimethyl – unspecified impurities : for each impurity, maximum
sulfoxide, practically insoluble in methanol. 0.10 per cent ;
– sum of impurities other than C and D (excluding embonic
IDENTIFICATION acid) : maximum 0.3 per cent ;
Infrared absorption spectrophotometry (2.2.24). – reporting threshold : 0.05 per cent.
Comparison : pyrantel embonate CRS.
Chlorides (2.4.4) : maximum 360 ppm.
TESTS To 0.46 g add 10 mL of dilute nitric acid R and 30 mL of
Related substances. Liquid chromatography (2.2.29). Prepare water R. Heat on a water-bath for 5 min. Cool, dilute to 50 mL
the solutions immediately before use and protect from light. with water R, mix well and filter.
Solvent mixture. Mix 5 volumes of glacial acetic acid R and Sulfates (2.4.13) : maximum 0.1 per cent.
5 volumes of water for chromatography R, then add 2 volumes To 0.50 g add 2.5 mL of dilute nitric acid R and dilute to 50 mL
of diethylamine R with cooling. with distilled water R. Heat on a water-bath for 5 min, shake
Test solution (a). Dissolve 0.800 g of the substance to be for 2 min, cool and filter.
examined in 7 mL of the solvent mixture and dilute to Iron (2.4.9) : maximum 75 ppm.
100.0 mL with acetonitrile R. Ignite 0.66 g at 800 ± 50 °C for 2 h. Dissolve the residue in
Test solution (b). Dilute 1.0 mL of test solution (a) to 10.0 mL 2.5 mL of dilute hydrochloric acid R with gentle heating for
with the mobile phase. 10 min. Cool and dilute to 50 mL with water R.

4478 See the information section on general monographs (cover pages)

EUROPEAN PHARMACOPOEIA 10.1 Pyrimethamine

Loss on drying (2.2.32): maximum 1.0 per cent, determined DEFINITION

on 1.000 g by drying in vacuo at 60 °C for 3 h.
Sulfated ash (2.4.14) : maximum 0.1 per cent, determined on
1.0 g.
ASSAY
To 0.450 g add 10 mL of acetic anhydride R and 50 mL of
glacial acetic acid R, heat at 50 °C and stir for 10 min. Allow
to cool (a clear solution is not obtained). Titrate with 0.1 M
perchloric acid, determining the end-point potentiometrically
(2.2.20). Carry out a blank titration.
1 mL of 0.1 M perchloric acid is equivalent to 59.47 mg of
C34H30N2O6S.
STORAGE
Protected from light.
IMPURITIES
Specified impurities : C, D.
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 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.
A. 1-methyl-2-[(Z)-2-(thiophen-2-yl)eth-1-en-1-yl]-1,4,5,6-
tetrahydropyrimidine,
5-(4-Chlorophenyl)-6-ethylpyrimidine-2,4-diamine.
Content : 99.0 per cent to 101.0 per cent (dried substance).
CHARACTERS
Appearance : white or almost white, crystalline powder or
colourless crystals.
Solubility : practically insoluble in water, slightly soluble in
ethanol (96 per cent).
IDENTIFICATION
First identification : B.
Second identification : A, C.
A. Melting point (2.2.14) : 239 °C to 243 °C.
B. Infrared absorption spectrophotometry (2.2.24).
Comparison : pyrimethamine CRS.
C. Thin-layer chromatography (2.2.27).
Solvent mixture : methanol R, methylene chloride R
(10:90 V/V).
Test solution. Dissolve 0.1 g of the substance to be
examined in the solvent mixture and dilute to 100 mL with
the solvent mixture.
Reference solution. Dissolve 0.1 g of pyrimethamine CRS in
the solvent mixture and dilute to 100 mL with the solvent
mixture.
Plate : TLC silica gel F254 plate R.
Mobile phase : methylene chloride R, propanol R, glacial
acetic acid R, toluene R (4:8:12:76 V/V/V/V).
Application : 20 μL.
Development : over 2/3 of the plate.
Drying : in air.
Detection : examine in ultraviolet light at 254 nm.
Results : the principal spot in the chromatogram obtained
with the test solution is similar in position and size to the
principal spot in the chromatogram obtained with the
reference solution.

B. (E)-N-[3-(methylamino)propyl]-3-(thiophen-2-yl)prop-2- TESTS
enamide, Solution S. Shake 1.0 g with 50 mL of carbon dioxide-free
water R for 2 min and filter.
Appearance of solution. Prepare the solution immediately
before use. Dissolve 0.25 g in a mixture of 1 volume of
C. thiophene-2-carbaldehyde, methanol R and 3 volumes of methylene chloride R and dilute
to 10 mL with the same mixture of solvents. The solution is
clear (2.2.1) and not more intensely coloured than reference
solution BY6 (2.2.2, Method II).
Acidity or alkalinity. To 10 mL of solution S add 0.05 mL of
phenolphthalein solution R1. The solution is colourless. Not
D. 1,2-dimethyl-1,4,5,6-tetrahydropyrimidine. more than 0.2 mL of 0.01 M sodium hydroxide is required to
change the colour of the indicator to pink. Add 0.4 mL of
0.01 M hydrochloric acid and 0.05 mL of methyl red solution R.
04/2020:0288 The solution is red or orange.
Related substances. Liquid chromatography (2.2.29).
Solvent mixture : mobile phase A, mobile phase B (50:50 V/V).
Test solution. Dissolve 10.0 mg of the substance to be
PYRIMETHAMINE examined in 4 mL of the solvent mixture using sonication and
dilute to 10.0 mL with the solvent mixture.
Pyrimethaminum Reference solution (a). Dissolve 10 mg of the substance to be
examined and 10 mg of pyrimethamine impurity B CRS in
50 mL of the solvent mixture using sonication and dilute to
100 mL with the solvent mixture.
Reference solution (b). Dilute 1.0 mL of the test solution to
100.0 mL with the solvent mixture. Dilute 1.0 mL of this
solution to 10.0 mL with the solvent mixture.
C12H13ClN4 Mr 248.7 Column :
[58-14-0] – size : l = 0.25 m, Ø = 4.6 mm ;

General Notices (1) apply to all monographs and other texts 4479