EUROPEAN PHARMACOPOEIA 5.

0 Sodium acetate trihydrate

IMPURITIES

E. R1 = CH3, R2 = H : (1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-
4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl]ethyl]-3,
7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl
(2S)-2-methylbutanoate (lovastatin),
F. R1 = H, R2 = CH3 : (1S,3R,7S,8S,8aR)-8-[2-[(2R,
4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl]ethyl]-
3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl
A. (3R,5R)-7-[(1S,2S,6R,8S,8aR)-8-[(2,2-dimethylbu- (2R)-2-methylbutanoate (epilovastatin),
tanoyl)oxy]-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphtha-
len-1-yl]-3,5-dihydroxyheptanoic acid (hydroxy acid),

B. (1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-(acetyloxy)-6- G. (1S,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxotetrahydro-
oxotetrahydro-2H-pyran-2-yl]ethyl]-3,7-dimethyl-1,2,3,7, 2H-pyran-2-yl]ethyl]-7-methyl-3-methylene-1,2,3,7,8,8a-
8,8a-hexahydronaphthalen-1-yl 2,2-dimethylbutanoate hexahydronaphthalen-1-yl 2,2-dimethylbutanoate.
(acetate ester),
01/2005:0411

SODIUM ACETATE TRIHYDRATE

Natrii acetas trihydricus

C. (1S,3R,7S,8S,8aR)-3,7-dimethyl-8-[2-[(2R)-6-oxo-
3,6-dihydro-2H-pyran-2-yl]ethyl]-1,2,3,7,8,8a- C2H3NaO2,3H2O Mr 136.1
hexahydronaphthalen-1-yl 2,2-dimethylbutanoate
(anhydrosimvastatin), DEFINITION
Sodium ethanoate trihydrate.
Content : 99.0 per cent to 101.0 per cent (dried substance).
CHARACTERS
Appearance : colourless crystals.
Solubility : very soluble in water, soluble in alcohol.
IDENTIFICATION
A. 1 ml of solution S (see Tests) gives reaction (b) of acetates
(2.3.1).
B. 1 ml of solution S gives reaction (a) of sodium (2.3.1).
C. It complies with the test for loss on drying (see Tests).
TESTS
D. (2R,4R)-2-[[(1S,2S,6R,8S,8aR)-8-[(2,2-dimethylbu-
tanoyl)oxy]-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaph- Solution S. Dissolve 10.0 g in carbon dioxide-free water R
thalen-1-yl]ethyl]-6-oxotetrahydro-2H-pyran-4-yl prepared from distilled water R and dilute to 100 ml with
(3R,5R)-7-[(1S,2S,6R,8S,8aR)-8-[(2,2-dimethylbu- the same solvent.
tanoyl)oxy]-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphtha- Appearance of solution. Solution S is clear (2.2.1) and
len-1-yl]-3,5-dihydroxyheptanoate (dimer), colourless (2.2.2, Method II).

General Notices (1) apply to all monographs and other texts 2415
Sodium alendronate EUROPEAN PHARMACOPOEIA 5.0

pH (2.2.3) : 7.5 to 9.0. 01/2005:1564

Dilute 5 ml of solution S to 10 ml with carbon dioxide-free corrected
water R.
Reducing substances. Dissolve 1.0 g in 100 ml of boiling
SODIUM ALENDRONATE
water R, add 5 ml of dilute sulphuric acid R and 0.5 ml of
0.002 M potassium permanganate, mix and boil gently for Natrii alendronas
5 min. The pink colour is not completely discharged.
Chlorides (2.4.4) : maximum 200 ppm.
2.5 ml of solution S diluted to 15 ml with water R complies
with the limit test for chlorides.
Sulphates (2.4.13) : maximum 200 ppm.
7.5 ml of solution S diluted to 15 ml with distilled water R C4H12NNaO7P2,3H2O Mr 325.1
complies with the limit test for sulphates. DEFINITION
Aluminium (2.4.17) : maximum 0.2 ppm, if intended for use Sodium alendronate contains not less than 98.0 per
in the manufacture of dialysis solutions. cent and not more than the equivalent of 102.0 per cent
Dissolve 20 g in 100 ml of water R and adjust to pH 6.0 by of (4-amino-1-hydroxybutylidene)bisphosphonic acid
the addition of 1 M hydrochloric acid (about 10 ml). The monosodium salt, calculated with reference to the dried
solution complies with the limit test for aluminium. Use substance.
as the reference solution a mixture of 2 ml of aluminium
CHARACTERS
standard solution (2 ppm Al) R, 10 ml of acetate buffer
solution pH 6.0 R and 98 ml of water R. To prepare the A white or almost white, crystalline powder, soluble in water,
blank, use a mixture of 10 ml of acetate buffer solution very slightly soluble in methanol, practically insoluble in
pH 6.0 R and 100 ml of water R. methylene chloride.
Arsenic (2.4.2) : maximum 2 ppm. IDENTIFICATION
0.5 g complies with limit test A. A. Examine by infrared absorption spectrophotometry
(2.2.24), comparing with the spectrum obtained with
Calcium and magnesium : maximum 50 ppm, calculated sodium alendronate CRS. Examine the substances
as Ca. prepared as discs.
To 200 ml of water R add 10 ml of ammonium chloride B. It gives reaction (a) of sodium (2.3.1).
buffer solution pH 10.0 R, 0.1 g of mordant black 11
triturate R, 2.0 ml of 0.05 M zinc chloride and, dropwise, TESTS
0.02 M sodium edetate until the colour changes from violet Solution S. Dissolve 0.5 g in carbon dioxide-free water R
to blue. Add to the solution 10.0 g of the substance to be prepared from distilled water R and dilute to 50 ml with the
examined and shake to dissolve. Titrate with 0.02 M sodium same solvent.
edetate until the blue colour is restored. Not more than
Appearance of solution. Solution S is clear (2.2.1) and not
0.65 ml of 0.02 M sodium edetate is required.
more intensely coloured than reference solution B7 or BY7
Heavy metals (2.4.8) : maximum 10 ppm. (2.2.2, Method II).
12 ml of solution S complies with limit test A. Prepare the pH (2.2.3). The pH of solution S is 4.0 to 5.0.
standard using lead standard solution (1 ppm Pb) R. 4-aminobutanoic acid. Examine by thin-layer
Iron (2.4.9) : maximum 10 ppm. chromatography (2.2.27), using a TLC silica gel plate R.
10 ml of solution S complies with the limit test for iron. Test solution. Dissolve 0.10 g of the substance to be
examined in water R and dilute to 10 ml with the same
Loss on drying (2.2.32) : 39.0 per cent to 40.5 per cent, solvent.
determined on 1.000 g by drying in an oven at 130 °C.
Reference solution (a). Dissolve 0.10 g of 4-aminobutanoic
Introduce the substance to be examined into the oven while
acid R in water R and dilute to 200 ml with the same solvent.
the latter is cold.
Reference solution (b). Dilute 1 ml of reference solution (a)
to 10 ml with water R.
ASSAY
Apply to the plate 5 µl of the test solution and 5 µl of
Dissolve 0.250 g in 50 ml of anhydrous acetic acid R, add reference solution (b). Allow the plate to dry in air. Develop
5 ml of acetic anhydride R, mix and allow to stand for over a path of 15 cm using a mixture of 20 volumes of
30 min. Using 0.3 ml of naphtholbenzein solution R as water R, 20 volumes of glacial acetic acid R and 60 volumes
indicator, titrate with 0.1 M perchloric acid until a green of butanol R. Dry the plate in a current of warm air. Spray
colour is obtained. with ninhydrin solution R and heat at 100 °C to 105 °C for
1 ml of 0.1 M perchloric acid is equivalent to 8.20 mg of 15 min. Any spots corresponding to 4-aminobutanoic acid
C2H3NaO2. in the chromatogram obtained with the test solution are not
more intense than the spot in the chromatogram obtained
STORAGE with reference solution (b) (0.5 per cent).
In an airtight container. Phosphate and phosphite. Examine the chromatograms
obtained in the assay. In the chromatogram obtained with
the test solution : the area of any peak corresponding to
LABELLING phosphate is not greater than that of the peak due to
The label states, where applicable, that the substance is phosphate in the chromatogram obtained with reference
suitable for use in the manufacture of dialysis solutions. solution (d) (0.5 per cent) ; the area of any peak corresponding

2416 See the information section on general monographs (cover pages)