Calcium dobesilate monohydrate

EUROPEAN PHARMACOPOEIA 8.0

Barium. To 10 mL of solution S add 1 mL of calcium sulfate

Heavy metals (2.4.8) : maximum 20 ppm.
12 mL of solution S complies with test A. Prepare the reference solution R. After at least 15 min, any opalescence in the
solution is not more intense than that in a mixture of 1 mL of
solution using lead standard solution (2 ppm Pb) R.
distilled water R and 10 mL of solution S.
ASSAY
Iron (2.4.9) : maximum 7 ppm, determined on solution S.
Dissolve 0.280 g in 100 mL of water R and carry out the
Magnesium and alkali metals : maximum 0.3 per cent.
complexometric titration of calcium (2.5.11).
To
a mixture of 20 mL of solution S and 80 mL of water R add
1 mL of 0.1 M sodium edetate is equivalent to 14.70 mg
2 g of ammonium chloride R and 2 mL of dilute ammonia R1,
of CaCl2,2H2O.
heat to boiling and pour into the boiling solution a hot
solution of 5 g of ammonium oxalate R in 75 mL of water R.
LABELLING
The label states, where applicable, that the substance is suitable Allow to stand for 4 h, dilute to 200 mL with water R and lter
through a suitable lter. To 100 mL of the ltrate add 0.5 mL
for use in the manufacture of dialysis solutions.
of sulfuric acid R. Evaporate to dryness on a water-bath and
ignite to constant mass at 600 50 C. The residue weighs a
STORAGE
maximum of 5 mg.
In an airtight container.
Heavy metals (2.4.8): maximum 15 ppm.
01/2008:0707 12 mL of solution S complies with test A. Prepare the reference
corrected 6.0 solution using lead standard solution (2 ppm Pb) R.

CALCIUM CHLORIDE HEXAHYDRATE

Calcii chloridum
CaCl2,6H2O
[7774-34-7]

ASSAY
Dissolve 0.200 g in 100 mL of water R. Carry out the
complexometric titration of calcium (2.5.11).
hexahydricum
1 mL of 0.1 M sodium edetate is equivalent to 21.91 mg
Mr 219.1 of CaCl2,6H2O.

DEFINITION
Content : 97.0 per cent to 103.0 per cent of CaCl2,6H2O.
CHARACTERS
Appearance : white or almost white, crystalline mass or
colourless crystals.
Solubility : very soluble in water, freely soluble in ethanol
(96 per cent).
It solidies at about 29 C.
IDENTIFICATION
A. Solution S (see Tests) gives reaction (a) of chlorides (2.3.1).
B. It gives the reactions of calcium (2.3.1).
C. It complies with the limits of the assay.
TESTS
Solution S. Dissolve 15.0 g in carbon dioxide-free water R
prepared from distilled water R and dilute to 100 mL with the
same solvent.
Appearance of solution. Solution S is clear (2.2.1) and not
more intensely coloured than reference solution Y6 (2.2.2,
Method II).
Acidity or alkalinity. To 10 mL of freshly prepared solution S
add 0.1 mL of phenolphthalein solution R. If the solution is red,
not more than 0.2 mL of 0.01 M hydrochloric acid is required
to discharge the colour and if the solution is colourless, not
more than 0.2 mL of 0.01 M sodium hydroxide is required to
turn it red.
Sulfates (2.4.13) : maximum 200 ppm.
Dilute 5 mL of solution S to 15 mL with distilled water R.
Aluminium. To 10 mL of solution S add 2 mL of ammonium
chloride solution R and 1 mL of dilute ammonia R1. Heat to
boiling. No turbidity or precipitate is formed.
If intended for use in the manufacture of dialysis solutions,
the above test is replaced by the following test for aluminium
(2.4.17) : maximum 1 ppm.
Prescribed solution. Dissolve 6 g in 100 mL of water R and add
10 mL of acetate buffer solution pH 6.0 R.
Reference solution. Mix 2 mL of aluminium standard solution
(2 ppm Al) R, 10 mL of acetate buffer solution pH 6.0 R and
98 mL of water R.
Blank solution. Mix 10 mL of acetate buffer solution pH 6.0 R
and 100 mL of water R.
General Notices (1) apply to all monographs and other texts

LABELLING
The label states, where applicable, that the substance is suitable
for use in the manufacture of dialysis solutions.
07/2008:1183
corrected 7.0

CALCIUM DOBESILATE
MONOHYDRATE
Calcii dobesilas monohydricus

C12H10CaO10S2,H2O
[20123-80-2]

Mr 436.4

DEFINITION
Calcium di(2,5-dihydroxybenzenesulfonate) monohydrate.
Content : 99.0 per cent to 101.0 per cent (anhydrous substance).
CHARACTERS
Appearance : white or almost white, hygroscopic powder.
Solubility : very soluble in water, freely soluble in anhydrous
ethanol, very slightly soluble in 2-propanol, practically
insoluble in methylene chloride.
IDENTIFICATION
A. Ultraviolet and visible absorption spectrophotometry
(2.2.25).
Test solution. Dissolve 0.100 g in water R and dilute to
200.0 mL with the same solvent. Dilute 5.0 mL of this
solution to 100.0 mL with water R.
Spectral range : 210-350 nm.
Absorption maxima : at 221 nm and 301 nm.
Specific absorbance at the absorption maximum at 301 nm :
174 to 181.
B. Mix 1 mL of ferric chloride solution R2, 1 mL of a freshly
prepared 10 g/L solution of potassium ferricyanide R
and 0.1 mL of nitric acid R. To this mixture add 5 mL of
freshly prepared solution S (see Tests) : a blue colour and a
precipitate are immediately produced.

1733

Calcium folinate

EUROPEAN PHARMACOPOEIA 8.0

C. 2 mL of freshly prepared solution S gives reaction (b) of

calcium (2.3.1).

1 mL of 0.1 M cerium sulfate is equivalent to 10.45 mg of

C12H10CaO10S2.

TESTS
Solution S. Dissolve 10.0 g in carbon dioxide-free water R and
dilute to 100 mL with the same solvent.
Appearance of solution. Solution S, when freshly prepared,
is clear (2.2.1) and colourless (2.2.2, Method II).
pH (2.2.3): 4.5 to 6.0 for solution S.
Related substances. Liquid chromatography (2.2.29). Keep
all solutions at 2-8 C.
Buffer solution. Dissolve 1.2 g of anhydrous sodium dihydrogen
phosphate R in 900 mL of water for chromatography R, adjust
to pH 6.5 with disodium hydrogen phosphate solution R and
dilute to 1000 mL with water for chromatography R.
Test solution. Dissolve 0.100 g of the substance to be examined
in water R and dilute to 10.0 mL with the same solvent.
Reference solution (a). Dilute 1.0 mL of the test solution to
100.0 mL with water R. Dilute 1.0 mL of this solution to
10.0 mL with water R.
Reference solution (b). Dissolve 10 mg of the substance to
be examined and 10 mg of hydroquinone R (impurity A) in
water R and dilute to 10 mL with the same solvent. Dilute
1 mL of this solution to 100 mL with water R.
Column :
size : l = 0.25 m, = 4.6 mm ;
stationary phase : spherical end-capped octadecylsilyl silica
gel for chromatography R (5 m).
Mobile phase : acetonitrile R1, buffer solution (10:90 V/V).
Flow rate : 0.8 mL/min.
Detection : spectrophotometer at 220 nm.
Injection : 10 L.
Run time : 2.5 times the retention time of dobesilate.
Relative retention with reference to dobesilate (retention
time = about 6 min) : impurity A = about 1.7.
System suitability : reference solution (b) :
resolution : minimum 8.0 between the peaks due to
dobesilate and impurity A.
Limits :
correction factor : for the calculation of content, multiply
the peak area of impurity A by 0.6 ;
impurity A : not more than the area of the principal peak
in the chromatogram obtained with reference solution (a)
(0.1 per cent) ;
unspecified impurities : for each impurity, not more than the
area of the principal peak in the chromatogram obtained
with reference solution (a) (0.10 per cent) ;
total : not more than twice the area of the principal peak
in the chromatogram obtained with reference solution (a)
(0.2 per cent) ;
disregard limit : 0.5 times the area of the principal peak in
the chromatogram obtained with reference solution (a)
(0.05 per cent).
Heavy metals (2.4.8) : maximum 15 ppm.
1.0 g complies with test C. Prepare the reference solution using
1.5 mL of lead standard solution (10 ppm Pb) R.
Iron (2.4.9) : maximum 10 ppm, determined on 10 mL of
solution S.
Water (2.5.12) : 4.0 per cent to 6.0 per cent, determined on
0.500 g.

STORAGE
In an airtight container, protected from light.

ASSAY
Dissolve 0.200 g in a mixture of 10 mL of water R and 40 mL
of dilute sulfuric acid R. Titrate with 0.1 M cerium sulfate,
determining the end-point potentiometrically (2.2.20).

1734

IMPURITIES
Specified impurities : A.

A. benzene-1,4-diol (hydroquinone).
01/2009:0978
corrected 7.0

CALCIUM FOLINATE
Calcii folinas

C20H21CaN7O7,xH2O

Mr 511.5 (anhydrous substance)

DEFINITION
Calcium (2S)-2-[[4-[[[(6RS)-2-amino-5-formyl-4-oxo1,4,5,6,7,8-hexahydropteridin-6-yl]methyl]amino]benzoyl]amino]pentanedioate.
Content :
calcium folinate (C20H21CaN7O7): 97.0 per cent to 102.0 per
cent (anhydrous substance) ;
calcium (Ca ; Ar 40.08) : 7.54 per cent to 8.14 per cent
(anhydrous substance).
It contains a variable quantity of water.
CHARACTERS
Appearance : white or light yellow, amorphous or crystalline,
hygroscopic powder.
Solubility : sparingly soluble in water, practically insoluble in
acetone and in ethanol (96 per cent).
The amorphous form may produce supersaturated solutions
in water.
IDENTIFICATION
First identification : A, B, D.
Second identification : A, C, D.
A. Specic optical rotation (see Tests).
B. Infrared absorption spectrophotometry (2.2.24).
Preparation : discs.
Comparison : calcium folinate CRS.
If the spectra obtained show differences, dissolve the
substance to be examined and the reference substance
separately in the minimum volume of water R and add
dropwise sufcient acetone R to produce a precipitate.
Allow to stand for 15 min, collect the precipitate by
centrifugation, wash the precipitate with 2 small quantities
of acetone R and dry. Record new spectra using the
residues.
C. Thin-layer chromatography (2.2.27).
Test solution. Dissolve 15 mg of the substance to be
examined in a 3 per cent V/V solution of ammonia R and
dilute to 5 mL with the same solvent.
See the information section on general monographs (cover pages)