EUROPEAN PHARMACOPOEIA 11.
0 2,4-Dichlorobenzyl alcohol
TESTS
Appearance. The substance to be examined is clear (2.2.1)
and not more intensely coloured than reference solution Y6
(2.2.2, Method II).
Acidity. Dissolve 20.0 g in 50 mL of ethanol (96 per cent) R
previously neutralised to phenolphthalein solution R1. Add
0.2 mL of phenolphthalein solution R1. Not more than 0.50 mL
of 0.1 M sodium hydroxide is required to change the colour of
the indicator.
Related substances. Gas chromatography (2.2.28).
Internal standard solution. Dissolve 60 mg of bibenzyl R
in methylene chloride R and dilute to 20 mL with the same
solvent.
Test solution (a). Dissolve 1.0 g of the substance to be
examined in methylene chloride R and dilute to 20.0 mL with
the same solvent.
Test solution (b). Dissolve 1.0 g of the substance to be
examined in methylene chloride R, add 2.0 mL of the internal
standard solution and dilute to 20.0 mL with methylene
chloride R.
Reference solution. To 1.0 mL of test solution (a) add 10.0 mL
of the internal standard solution and dilute to 100.0 mL with
methylene chloride R.
Column :
– material : glass ;
– size : l = 1.5 m, Ø = 4 mm ;
– stationary phase : silanised diatomaceous earth for gas
chromatography R (150-180 μm) impregnated with 3 per
cent m/m of phenyl(50)methyl(50)polysiloxane R.
Carrier gas : nitrogen for chromatography R.
Flow rate : 30 mL/min.
Temperature :
– column : 190 °C ;
– injection port and detector : 225 °C.
Detection : flame ionisation.
Injection : 1 μL.
Run time : 3 times the retention time of dibutyl phthalate.
Elution order : bibenzyl, dibutyl phthalate.
Retention time : dibutyl phthalate = about 12 min.
System suitability :
– resolution : minimum 12 between the peaks due to bibenzyl
and dibutyl phthalate in the chromatogram obtained with
the reference solution ;
– in the chromatogram obtained with test solution (a), there
is no peak with the same retention time as the internal
standard.
Limit :
– total : calculate the ratio (R) of the area of the peak due
to dibutyl phthalate to the area of the peak due to the
internal standard from the chromatogram obtained with
the reference solution ; from the chromatogram obtained
with test solution (b), calculate the ratio of the sum of the
areas of any peaks, apart from the principal peak and the
peak due to the internal standard, to the area of the peak
due to the internal standard : this ratio is not greater than
R (1.0 per cent).
Water (2.5.12): maximum 0.2 per cent, determined on 10.00 g.
Sulfated ash (2.4.14) : maximum 0.1 per cent, determined on
1.0 g.
ASSAY
Introduce 0.750 g into a 250 mL borosilicate glass flask. Add
25.0 mL of 0.5 M alcoholic potassium hydroxide and a few
glass beads. Heat in a water-bath under a reflux condenser
for 1 h. Add 1 mL of phenolphthalein solution R1 and titrate
immediately with 0.5 M hydrochloric acid until the colour
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changes from red to colourless. Carry out a blank titration.
Calculate the volume of potassium hydroxide used in the
saponification.
1 mL of 0.5 M alcoholic potassium hydroxide is equivalent to
69.59 mg of C16H22O4.
STORAGE
In an airtight container.
04/2014:2410
2,4-DICHLOROBENZYL ALCOHOL
Alcohol 2,4-dichlorobenzylicus
C7H6Cl2O Mr 177.0
[1777-82-8]
DEFINITION
(2,4-Dichlorophenyl)methanol.
Content : 98.0 per cent to 102.0 per cent (anhydrous substance).
CHARACTERS
Appearance : white or almost white, crystalline powder.
Solubility : very slightly soluble in water, very soluble in
ethanol (96 per cent).
mp : about 59 °C.
IDENTIFICATION
Infrared absorption spectrophotometry (2.2.24).
Comparison : 2,4-dichlorobenzyl alcohol CRS.
TESTS
Related substances. Liquid chromatography (2.2.29).
Solvent mixture : acetonitrile R1, water R (50:50 V/V).
Buffer solution. Dissolve 0.68 g of potassium dihydrogen
phosphate R in 900 mL of water R, adjust to pH 3.0 with
phosphoric acid R and dilute to 1000.0 mL with water R.
Test solution (a). Dissolve 0.100 g of the substance to be
examined in 10.0 mL of acetonitrile R1 and dilute to 50.0 mL
with the solvent mixture.
Test solution (b). Dilute 5.0 mL of test solution (a) to 50.0 mL
with the solvent mixture.
Reference solution (a). Dilute 1.0 mL of test solution (a) to
100.0 mL with the solvent mixture. Dilute 1.0 mL of this
solution to 10.0 mL with the solvent mixture.
Reference solution (b). Dissolve 20.0 mg of 2,4-dichlorobenzyl
alcohol impurity A CRS and 20.0 mg of 2,4-dichlorobenzyl
alcohol impurity C CRS in 100.0 mL of acetonitrile R1. Dilute
1.0 mL of the solution to 100.0 mL with the solvent mixture.
Reference solution (c). Dissolve 0.100 g of 2,4-dichlorobenzyl
alcohol CRS in 10.0 mL of acetonitrile R1 and dilute to 50.0 mL
with the solvent mixture. Dilute 5.0 mL of the solution to
50.0 mL with the solvent mixture.
Column :
– size : l = 0.15 m, Ø = 4.6 mm ;
– stationary phase : end-capped octadecylsilyl silica gel for
chromatography R (5 μm) ;
– temperature : 30 °C.
Mobile phase :
– mobile phase A : methanol R2, acetonitrile R1, buffer
solution (20:30:50 V/V/V) ;
2517
Diclazuril for veterinary use EUROPEAN PHARMACOPOEIA 11.0

– mobile phase B : acetonitrile R1 ;

Time Mobile phase A Mobile phase B
(min) (per cent V/V) (per cent V/V)
0-7 100 0
C. (3,4-dichlorophenyl)methanol,
7 - 17 100 → 20 0 → 80

17 - 30 20 80

Flow rate : 1.2 mL/min.

Detection : spectrophotometer at 214 nm.
Injection : 10 μL of test solution (a) and reference solutions (a) D. 2,4-dichlorobenzyl acetate,
and (b).
Relative retention with reference to 2,4-dichlorobenzyl alcohol
(retention time = about 7 min) : impurity C = about 0.87 ;
impurity A = about 0.91.
E. 2,4-dichlorobenzoic acid,
System suitability : reference solution (b) :
– peak-to-valley ratio : minimum 4, where Hp = height above
the baseline of the peak due to impurity C and Hv = height
above the baseline of the lowest point of the curve
separating this peak from the peak due to impurity A. F. 2,4-dichlorobenzaldehyde,
Calculation of percentage contents :
– for each impurity, use the concentration of
2,4-dichlorobenzyl alcohol in reference solution (a).
Limits : G. 1,1′-(oxydimethylene)bis(2,4-dichlorobenzene).
– unspecified impurities : for each impurity, maximum
0.10 per cent ; 01/2008:1718
– total : maximum 0.3 per cent ; corrected 11.0
– reporting threshold : 0.05 per cent.
Water (2.5.32) : maximum 0.2 per cent, determined on 0.500 g
using the evaporation technique :
– temperature : 120 °C.
DICLAZURIL FOR VETERINARY USE
Sulfated ash (2.4.14) : maximum 0.1 per cent, determined on
1.0 g. Diclazurilum ad usum veterinarium
ASSAY
Liquid chromatography (2.2.29) as described in the test for
related substances with the following modification.
Injection : test solution (b) and reference solution (c).
Calculate the percentage content of C7H6Cl2O taking
into account the assigned content of 2,4-dichlorobenzyl C17H9Cl3N4O2 Mr 407.6
alcohol CRS. [101831-37-2]
IMPURITIES DEFINITION
Other detectable impurities (the following substances would, (RS)-(4-Chlorophenyl)[2,6-dichloro-4-(3,5-dioxo-4,5-
if present at a sufficient level, be detected by one or other of dihydro-1,2,4-triazin-2(3H)-yl)phenyl]acetonitrile.
the tests in the monograph. They are limited by the general Content : 99.0 per cent to 101.0 per cent (dried substance).
acceptance criterion for other/unspecified impurities and/or
by the general monograph Substances for pharmaceutical CHARACTERS
use (2034). It is therefore not necessary to identify these Appearance : white or light yellow powder.
impurities for demonstration of compliance. See also 5.10. Solubility : practically insoluble in water, sparingly soluble in
Control of impurities in substances for pharmaceutical use) : dimethylformamide, practically insoluble in ethanol (96 per
A, B, C, D, E, F, G. cent) and methylene chloride.
IDENTIFICATION
Infrared absorption spectrophotometry (2.2.24).
Comparison : Ph. Eur. reference spectrum of diclazuril.
A. (2,5-dichlorophenyl)methanol, TESTS
Related substances. Liquid chromatography (2.2.29).
Test solution. Dissolve 20.0 mg of the substance to be
examined in dimethylformamide R and dilute to 20.0 mL with
the same solvent.
Reference solution (a). Dissolve 5 mg of diclazuril for system
suitability CRS in dimethylformamide R and dilute to 5.0 mL
B. (2,6-dichlorophenyl)methanol, with the same solvent.

2518 See the information section on general monographs (cover pages)

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