EUROPEAN PHARMACOPOEIA 11.

0 Calcium hydrogen phosphate

Bacterial endotoxins (2.6.14) : less than 167 IU/g. residue at 70 °C for 1 h. The residue weighs a maximum of
Microbial contamination 5 mg.
TAMC : acceptance criterion 102 CFU/g (2.6.12). Chlorides (2.4.4) : maximum 500 ppm.
Dissolve 0.1 g in a mixture of 2 mL of acetic acid R and 8 mL
ASSAY of water R and dilute to 15 mL with water R.
Dissolve 0.350 g in 20 mL of hot water R, allow to cool and Phosphates (2.4.11) : maximum 400 ppm.
dilute to 300 mL with water R. Carry out the complexometric
titration of calcium (2.5.11). Use 50 mg of calconecarboxylic Dilute 2.5 mL of solution S to 100 mL with water R.
acid triturate R. Sulfates (2.4.13) : maximum 0.1 per cent, determined on
1 mL of 0.1 M sodium edetate is equivalent to 44.84 mg solution S.
of C12H22CaO14,H2O. Arsenic (2.4.2, Method A) : maximum 3 ppm.
Dissolve 0.33 g in water R and dilute to 25 mL with the same
01/2017:0980 solvent.
Iron (2.4.9) : maximum 50 ppm, detemined on 0.20 g.
Loss on drying (2.2.32) : maximum 12.0 per cent, determined
on 1.000 g by drying in an oven at 150 °C for 4 h.

CALCIUM GLYCEROPHOSPHATE ASSAY

Dissolve 0.200 g in water R. Carry out the complexometric
Calcii glycerophosphas titration of calcium (2.5.11).
1 mL of 0.1 M sodium edetate is equivalent to 4.008 mg of Ca.
C3H7CaO6P Mr 210.1
01/2022:0981
DEFINITION
Mixture in variable proportions of the calcium
salt of (RS)-2,3-dihydroxypropyl phosphate and of
2-hydroxy-1-(hydroxymethyl)ethyl phosphate which may be
hydrated.
Content : 18.6 per cent to 19.4 per cent of Ca (dried substance). CALCIUM HYDROGEN PHOSPHATE(1)
CHARACTERS Calcii hydrogenophosphas
Appearance : white or almost white powder, hygroscopic.
Solubility : sparingly soluble in water, practically insoluble in CaHPO4 Mr 136.1
ethanol (96 per cent). [7757-93-9]
IDENTIFICATION DEFINITION
A. Mix 1 g with 1 g of potassium hydrogen sulfate R in Content : 97.5 per cent to 102.5 per cent.
a test tube fitted with a glass tube. Heat strongly and
direct the white vapour towards a piece of filter paper ♦CHARACTERS
impregnated with a freshly prepared 10 g/L solution of Appearance : white or almost white, crystalline powder, or
sodium nitroprusside R. The filter paper develops a blue colourless crystals.
colour in contact with piperidine R. Solubility : practically insoluble in water and in ethanol (96 per
B. Ignite 0.1 g in a crucible. Take up the residue with 5 mL of cent). It dissolves in dilute hydrochloric acid and in dilute
nitric acid R and heat on a water-bath for 1 min. Filter. The nitric acid.♦
filtrate gives reaction (b) of phosphates (2.3.1).
IDENTIFICATION
C. It gives reaction (b) of calcium (2.3.1).
A. Dissolve with heating 0.1 g in 10 mL of dilute hydrochloric
TESTS acid R. Add 2.5 mL of dilute ammonia R1, shake, and add
Solution S. Dissolve 1.5 g at room temperature in carbon 5 mL of a 35 g/L solution of ammonium oxalate R. A white
dioxide-free water R prepared from distilled water R and dilute precipitate is produced.
to 150 mL with the same solvent. B. Dissolve 0.1 g in 5 mL of dilute nitric acid R, add 2 mL of
ammonium molybdate solution R and heat at 70 °C for
Appearance of solution. Solution S is not more opalescent 1-2 min. A yellow precipitate is produced.
than reference suspension III (2.2.1).
◊C. It complies with the limits of the assay.◊
Acidity or alkalinity. To 100 mL of solution S add 0.1 mL of
phenolphthalein solution R. Not more than 1.5 mL of 0.1 M TESTS
hydrochloric acid or 0.5 mL of 0.1 M sodium hydroxide is ♦Solution S. Dissolve 2.5 g in 20 mL of dilute hydrochloric
required to change the colour of the indicator. acid R, filter if necessary and add dilute ammonia R1 until a
Citric acid. Shake 5.0 g with 20 mL of carbon dioxide-free precipitate is formed. Add just sufficient dilute hydrochloric
water R and filter. To the filtrate add 0.15 mL of sulfuric acid R acid R to dissolve the precipitate and dilute to 50 mL with
and filter again. To the filtrate add 5 mL of mercuric sulfate distilled water R.♦
solution R and heat to boiling. Add 0.5 mL of a 3.2 g/L solution Acid-insoluble substances : maximum 0.2 per cent.
of potassium permanganate R and again heat to boiling. No
precipitate is formed. Dissolve 5.0 g in 40 mL of water R, add 10 mL of hydrochloric
acid R and heat to boiling for 5 min. Cool, then collect the
Glycerol and ethanol (96 per cent)-soluble substances : insoluble substances using ashless filter paper. Wash with
maximum 0.5 per cent. water R until turbidity is no longer produced when silver
Shake 1.000 g with 25 mL of ethanol (96 per cent) R for 1 min. nitrate solution R2 is added. Ignite the residue and the filter
Filter. Evaporate the filtrate on a water-bath and dry the paper at 600 ± 50 °C. The residue weighs not more than 10 mg.
(1) This monograph has undergone the process of Pharmacopoeial harmonisation. See chapter 5.8. Pharmacopoeial harmonisation.

General Notices (1) apply to all monographs and other texts 2175
Calcium hydrogen phosphate dihydrate EUROPEAN PHARMACOPOEIA 11.0

Carbonates. Shake 1.0 g with 5 mL of carbon dioxide-free ASSAY

water R and add 2 mL of hydrochloric acid R. No effervescence Dissolve 0.4 g in 12 mL of dilute hydrochloric acid R by heating
is produced. on a water bath if necessary and dilute to 200.0 mL with
Chlorides : maximum 0.25 per cent. water R. To 20.0 mL of this solution add 25.0 mL of 0.02 M
sodium edetate, 50 mL of water R, 5 mL of ammonium chloride
Test solution. Dissolve 0.20 g in a mixture of 20 mL of water R buffer solution pH 10.7 R and about 25 mg of mordant black 11
and 13 mL of dilute nitric acid R by warming if necessary, triturate R. Titrate the excess of sodium edetate with 0.02 M
dilute to 100 mL with water R and filter if necessary. Use zinc sulfate. Carry out a blank titration.
50 mL of this solution.
1 mL of 0.02 M sodium edetate is equivalent to 2.721 mg
Reference solution. To 0.70 mL of 0.01 M hydrochloric acid, of CaHPO4.
add 6 mL of dilute nitric acid R and dilute to 50 mL with
water R. ◊FUNCTIONALITY-RELATED CHARACTERISTICS
Add 1 mL of silver nitrate solution R2 to the test solution and This section provides information on characteristics that are
to the reference solution and mix. After standing for 5 min recognised as being relevant control parameters for one or
protected from light, any opalescence in the test solution, by more functions of the substance when used as an excipient
viewing vertically or horizontally against a black background, (see chapter 5.15). Some of the characteristics described in
is not more intense than that in the reference solution. the Functionality-related characteristics section may also be
present in the mandatory part of the monograph since they
♦Fluorides : maximum 100 ppm. also represent mandatory quality criteria. In such cases, a
Potentiometry (2.2.36, Method II). cross-reference to the tests described in the mandatory part is
included in the Functionality-related characteristics section.
Chelating solution. Dissolve 45 g of cyclohexylenedinitrilotetra- Control of the characteristics can contribute to the quality
acetic acid R in 75 mL of sodium hydroxide solution R and of a medicinal product by improving the consistency of the
dilute to 250 mL with water R. manufacturing process and the performance of the medicinal
Test solution. Dissolve 1.000 g in 4 mL of hydrochloric acid R1, product during use. Where control methods are cited, they are
add 20 mL of chelating solution, 2.7 mL of glacial acetic acid R recognised as being suitable for the purpose, but other methods
and 2.8 g of sodium chloride R, adjust to pH 5-6 with sodium can also be used. Wherever results for a particular characteristic
hydroxide solution R and dilute to 50.0 mL with water R. are reported, the control method must be indicated.
The following characteristics may be relevant for calcium
Reference solution. Dissolve 4.42 g of sodium fluoride R, hydrogen phosphate used as filler in tablets and capsules.
previously dried at 300 °C for 12 h, in water R and dilute
to 1000.0 mL with the same solvent. Dilute 50.0 mL of this Particle-size distribution (2.9.31 or 2.9.38).
solution to 500.0 mL with total-ionic-strength-adjustment Bulk and tapped density (2.9.34).
buffer R (200 ppm F).
Powder flow (2.9.36).◊
Indicator electrode : fluoride-selective.
Reference electrode : silver-silver chloride.
01/2022:0116
Carry out the measurement on 20.0 mL of the test solution.
Add at least 3 times 0.10 mL of the reference solution and
carry out the measurement after each addition. Calculate the
concentration of fluorides using the calibration curve.♦
Sulfates : maximum 0.5 per cent.
CALCIUM HYDROGEN PHOSPHATE
Test solution. Dissolve 0.5 g in a mixture of 5 mL of water R
and 5 mL of dilute hydrochloric acid R and dilute to 100 mL DIHYDRATE(2)
with water R. Filter if necessary. To 20 mL of this solution,
add 1 mL of dilute hydrochloric acid R and dilute to 50 mL Calcii hydrogenophosphas dihydricus
with water R.
Reference solution. To 1.0 mL of 0.005 M sulfuric acid, add CaHPO4,2H2O Mr 172.1
1 mL of dilute hydrochloric acid R and dilute to 50 mL with [7789-77-7]
water R. Filter if necessary.
DEFINITION
To the test solution and to the reference solution, add 2 mL of Content : 98.0 per cent to 105.0 per cent.
a 120 g/L solution of barium chloride R and allow to stand
for 10 min. Any opalescence in the test solution, by viewing ♦CHARACTERS
vertically or horizontally against a black background, is not Appearance : white or almost white, crystalline powder.
more intense than that in the reference solution.
Solubility : practically insoluble in water and in ethanol (96 per
♦Arsenic (2.4.2, Method A) : maximum 10 ppm, determined cent). It dissolves in dilute hydrochloric acid and in dilute
on 2 mL of solution S.♦ nitric acid.♦
Barium. To 0.5 g, add 10 mL of water R and heat to boiling.
While stirring, add 1 mL of hydrochloric acid R dropwise. IDENTIFICATION
Allow to cool and filter if necessary. Add 2 mL of a 10 g/L A. Dissolve with heating 0.1 g in 10 mL of dilute hydrochloric
solution of dipotassium sulfate R and allow to stand for 10 min. acid R. Add 2.5 mL of dilute ammonia R1, shake and add
No turbidity is produced. 5 mL of a 35 g/L solution of ammonium oxalate R. A white
precipitate is produced.
♦Iron (2.4.9) : maximum 400 ppm.
B. Dissolve 0.1 g in 5 mL of dilute nitric acid R, add 2 mL of
Dilute 0.5 mL of solution S to 10 mL with water R.♦ ammonium molybdate solution R and heat at 70 °C for
Loss on ignition : 6.6 per cent to 8.7 per cent, determined on 2 min. A yellow precipitate is produced.
1.000 g to constant mass at 800-825 °C. ◊C. It complies with the limits of the assay.◊
(2) This monograph has undergone pharmacopoeial harmonisation. See chapter 5.8. Pharmacopoeial harmonisation.

2176 See the information section on general monographs (cover pages)