EUROPEAN PHARMACOPOEIA 9.
0 Potassium hydrogen aspartate hemihydrate
Test solution. Dissolve 1.00 g of the substance to be examined
in water R and dilute to 100.0 mL with the same solvent.
Reference solutions. Prepare the reference solutions using the
following solution, diluted as necessary with water R : dissolve
0.5084 g of sodium chloride R, previously dried at 100-105 °C
for 3 h, in water R and dilute to 1000.0 mL with the same
solvent (200 μg of Na per millilitre).
Wavelength : 589 nm.
Loss on drying (2.2.32): maximum 2.0 per cent, determined
on 1.000 g by drying in an oven at 125-130 °C.
ASSAY
Dissolve 1.000 g in 50 mL of carbon dioxide-free water R.
Titrate with carbonate-free 1 M sodium hydroxide,
determining the end-point potentiometrically (2.2.20).
1 mL of 1 M sodium hydroxide is equivalent to 0.1361 g
of KH2PO4.
LABELLING
The label states, where applicable, that the substance is suitable
for use in the manufacture of parenteral preparations.
01/2017:2076
POTASSIUM HYDROGEN ASPARTATE
HEMIHYDRATE
Kalii hydrogenoaspartas hemihydricus
C4H6KNO4,½H2O Mr 180.2
DEFINITION
Potassium hydrogen (2S)-2-aminobutanedioate hemihydrate.
Content : 99.0 per cent to 101.0 per cent (anhydrous substance).
CHARACTERS
Appearance : white or almost white, powder or crystalline
powder, or colourless crystals.
Solubility : very soluble in water, practically insoluble in
alcohol and in methylene chloride.
IDENTIFICATION
A. Specific optical rotation (see Tests).
B. Examine the chromatograms obtained in the test for
ninhydrin-positive substances.
Results : the principal spot in the chromatogram obtained
with test solution (b) is similar in position, colour and size
to the principal spot in the chromatogram obtained with
reference solution (a).
C. It gives reaction (b) of potassium (2.3.1).
TESTS
Solution S. Dissolve 2.5 g in carbon dioxide-free water R
prepared from distilled water R and dilute to 100 mL with the
same solvent.
General Notices (1) apply to all monographs and other texts
Appearance of solution. Solution S is clear (2.2.1) and
colourless (2.2.2, Method II).
pH (2.2.3): 6.0 to 7.5 for solution S.
Specific optical rotation (2.2.7) : + 18.0 to + 20.5 (anhydrous
substance).
Dissolve 0.50 g in a mixture of equal volumes of hydrochloric
acid R and water R and dilute to 25.0 mL with the same
mixture of solvents.
Ninhydrin-positive substances. Thin-layer chromatography
(2.2.27).
Test solution (a). Solution S.
Test solution (b). Dilute 1.0 mL of solution S to 10.0 mL with
water R.
Reference solution (a). Dissolve 25 mg of potassium hydrogen
aspartate hemihydrate CRS in water R and dilute to 10 mL
with the same solvent.
Reference solution (b). Dilute 1.0 mL of test solution (b) to
20.0 mL with water R.
Reference solution (c). Dissolve 10 mg of glutamic acid CRS
and 10 mg of the substance to be examined in water R and
dilute to 25 mL with the same solvent.
Plate : TLC silica gel plate R.
Mobile phase : glacial acetic acid R, water R, butanol R
(20:20:60 V/V/V).
Application : 5 μL.
Development : over 2/3 of the plate.
Drying : in air.
Detection : spray with ninhydrin solution R and heat at
100-105 °C for 15 min.
System suitability : reference solution (c) :
– the chromatogram shows 2 clearly separated principal
spots.
Limits : test solution (a):
– any impurity : any spot, apart from the principal spot, is not
more intense than the spot in the chromatogram obtained
with reference solution (b) (0.5 per cent).
Chlorides (2.4.4) : maximum 200 ppm.
To 10 mL of solution S add 5 mL of water R.
Sulfates (2.4.13): maximum 500 ppm.
To 12 mL of solution S add 3 mL of distilled water R.
Ammonium (2.4.1, Method B): maximum 200 ppm,
determined on 50 mg.
Prepare the standard using 0.1 mL of ammonium standard
solution (100 ppm NH4) R.
Iron (2.4.9) : maximum 30 ppm.
In a separating funnel, dissolve 0.33 g in 10 mL of dilute
hydrochloric acid R. Shake with 3 quantities, each of 10 mL, of
methyl isobutyl ketone R1, shaking for 3 min each time. To the
combined organic layers add 10 mL of water R and shake for
3 min. The aqueous layer complies with the limit test for iron.
Water (2.5.12) : 4.0 per cent to 6.0 per cent, determined on
0.200 g.
Dissolve the substance to be examined in 10 mL of
formamide R1 and add 10 mL of anhydrous methanol R.
ASSAY
Dissolve 70.0 mg in 5 mL of anhydrous formic acid R, add
50 mL of anhydrous acetic acid R. Titrate with 0.1 M perchloric
acid, determining the end-point potentiometrically (2.2.20).
1 mL of 0.1 M perchloric acid is equivalent to 8.56 mg of
C4H6KNO4.
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