Diethyl phthalate
EUROPEAN PHARMACOPOEIA 8.0
04/2008:0897
Other detectable impurities (the following substances would,
if present at a sufcient level, be detected by one or other of
the tests in the monograph. They are limited by the general
acceptance criterion for other/unspecied 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) : H, I.
A. 1,7-dihydro-6H-purin-6-one (hypoxanthine),
DIETHYL PHTHALATE
Diethylis phthalas
C12H14O4
[84-66-2]
Mr 222.2
DEFINITION
Diethyl benzene-1,2-dicarboxylate.
Content : 99.0 per cent m/m to 101.0 per cent m/m.
CHARACTERS
Appearance : clear, colourless or very slightly yellow, oily
liquid.
Solubility : practically insoluble in water, miscible with ethanol
(96 per cent).
B. R = R = OH : 9--D-ribofuranosyl-1,9-dihydro-6H-purin6-one (inosine),
C. R = H, R = OH : 9-(2-deoxy--D-erythro-pentofuranosyl)1,9-dihydro-6H-purin-6-one (2-deoxyinosine),
D. R = OH, R = H : 9-(3-deoxy--D-erythro-pentofuranosyl)1,9-dihydro-6H-purin-6-one (3-deoxyinosine),
E. R + R = O : 9-(2,3-anhydro--D-ribofuranosyl)-1,9dihydro-6H-purin-6-one (2,3-anhydroinosine),
F. 9-(2,3-dideoxy--D-glycero-pent-2-enofuranosyl)1,9-dihydro-6H-purin-6-one (2,3-dideoxy-2,3didehydroinosine),
G. R = OH : 9-(2,3-dideoxy--D-glycero-pentofuranosyl)-9Hpurin-6-amine (2,3-dideoxyadenosine),
H. R = H : 9-(2,3,5-trideoxy--D-glycero-pentofuranosyl)-9Hpurin-6-amine (2,3,5-trideoxyadenosine),
I. 9-(2,3-dideoxy--D-glycero-pent-2-enofuranosyl)-9Hpurin-6-amine (2,3-dideoxy-2,3-didehydroadenosine).
General Notices (1) apply to all monographs and other texts
IDENTIFICATION
First identification : B, C.
Second identification : A, D, E.
A. Relative density (2.2.5) : 1.117 to 1.121.
B. Refractive index (2.2.6) : 1.500 to 1.505.
C. Infrared absorption spectrophotometry (2.2.24).
Preparation : thin lms.
Comparison : diethyl phthalate CRS.
D. Thin-layer chromatography (2.2.27).
Test solution. Dissolve 50 mg of the substance to be
examined in ether R and dilute to 10 mL with the same
solvent.
Reference solution. Dissolve 50 mg of diethyl phthalate CRS
in ether R and dilute to 10 mL with the same solvent.
Plate : TLC silica gel GF254 plate R.
Mobile phase : heptane R, ether R (30:70 V/V).
Application : 10 L.
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.
E. To about 0.1 mL add 0.25 mL of sulfuric acid R and 50 mg
of resorcinol R. Heat on a water-bath for 5 min. Allow to
cool. Add 10 mL of water R and 1 mL of strong sodium
hydroxide solution R. The solution becomes yellow or
brownish-yellow and shows green uorescence.
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 0.1 mL
of 0.1 M sodium hydroxide is required to change the colour of
the indicator to pink.
Related substances. Gas chromatography (2.2.28).
Internal standard solution. Dissolve 60 mg of naphthalene R
in methylene chloride R and dilute to 20 mL with the same
solvent.
2041
Diethylcarbamazine citrate
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.
EUROPEAN PHARMACOPOEIA 8.0
01/2008:0271
DIETHYLCARBAMAZINE CITRATE
Diethylcarbamazini citras
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 = 2 m, = 2 mm ;
stationary phase : silanised diatomaceous earth for gas
chromatography R (150-180 m) impregnated with 3 per
cent m/m of polymethylphenylsiloxane R.
Carrier gas : nitrogen for chromatography R.
Flow rate : 30 mL/min.
Temperature :
column : 150 C ;
injection port and detector : 225 C.
Detection : ame ionisation.
Injection : 1 L.
Run time : 3 times the retention time of diethyl phthalate.
Elution order : naphthalene, diethyl phtalate.
System suitability :
resolution : minimum 10 between the peaks due to
naphthalene and diethyl 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 diethyl 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 10.0 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 ask. Add
25.0 mL of 0.5 M alcoholic potassium hydroxide and a few
glass beads. Boil in a water-bath under a reux condenser
for 1 h. Add 1 mL of phenolphthalein solution R1 and titrate
immediately with 0.5 M hydrochloric acid. Carry out a blank
titration. Calculate the volume of 0.5 M alcoholic potassium
hydroxide used in the saponication.
1 mL of 0.5 M alcoholic potassium hydroxide is equivalent to
55.56 mg of C12H14O4.
STORAGE
In an airtight container.
2042
C16H29N3O8
[1642-54-2]
Mr 391.4
DEFINITION
N,N-Diethyl-4-methylpiperazine-1-carboxamide dihydrogen
2-hydroxypropane-1,2,3-tricarboxylate.
Content : 98.0 per cent to 102.0 per cent (dried substance).
CHARACTERS
Appearance : white or almost white, crystalline powder, slightly
hygroscopic.
Solubility : very soluble in water, soluble in ethanol (96 per
cent), practically insoluble in acetone.
mp : about 138 C, with decomposition.
IDENTIFICATION
First identification : A, C.
Second identification : B, C.
A. Infrared absorption spectrophotometry (2.2.24).
Comparison : diethylcarbamazine citrate CRS.
B. Examine the chromatograms obtained in the test for
impurities A and B.
Results : the principal spot in the chromatogram obtained
with the test solution is similar in position, colour and size
to the principal spot in the chromatogram obtained with
reference solution (a).
C. Dissolve 0.1 g in 5 mL of water R. The solution gives the
reaction of citrates (2.3.1).
TESTS
Solution S. Shake 2.5 g with water R until dissolved and dilute
to 25 mL with the same solvent.
Appearance of solution. Solution S is not more opalescent
than reference suspension II (2.2.1) and not more intensely
coloured than reference solution BY6 (2.2.2, Method II).
Impurities A and B. Thin-layer chromatography (2.2.27).
Test solution. Dissolve 0.5 g of the substance to be examined
in methanol R and dilute to 10 mL with the same solvent.
Reference solution (a). Dissolve 0.1 g of diethylcarbamazine
citrate CRS in methanol R and dilute to 2.0 mL with the same
solvent.
Reference solution (b). Dissolve 10 mg of methylpiperazine R
(impurity A) in methanol R and dilute to 100 mL with the
same solvent.
Reference solution (c). Dissolve 10 mg of dimethylpiperazine R
(impurity B) in methanol R and dilute to 100 mL with the
same solvent.
Plate : TLC silica gel plate R.
Mobile phase : concentrated ammonia R, methyl ethyl ketone R,
methanol R (5:30:65 V/V/V).
Application : 10 L.
Development : over 2/3 of the plate.
Drying : at 100-105 C.
Detection : expose to iodine vapour for 30 min.
Retardation factors : impurity A = about 0.2 ; impurity B = about
0.5.
See the information section on general monographs (cover pages)
