Glucose monohydrate EUROPEAN PHARMACOPOEIA 9.1
Injection: 20 μL of the test solution and reference solutions (b),
(c) and (d).
Run time: 1.5 times the retention time of glucose.
Relative retention with reference to glucose (retention
time = about 21 min): impurity C = about 0.7; impurities A
and B = about 0.8; impurity D = about 1.3.
System suitability: reference solution (d):
– resolution: minimum 1.3 between the peaks due to
impurities C and A.
Limits:
– sum of impurities A and B: not more than the area of
the principal peak in the chromatogram obtained with
reference solution (b) (0.4 per cent);
– impurity C: not more than 0.5 times the area of the
principal peak in the chromatogram obtained with
reference solution (b) (0.2 per cent);
– impurity D: not more than 3 times the area of the principal
peak in the chromatogram obtained with reference
solution (c) (0.15 per cent);
– unspecified impurities: for each impurity, not more than
twice the area of the principal peak in the chromatogram
obtained with reference solution (c) (0.10 per cent);
– total: not more than 1.25 times the area of the principal
peak in the chromatogram obtained with reference
solution (b) (0.5 per cent);
– disregard limit: the area of the principal peak in the
chromatogram obtained with reference solution (c)
(0.05 per cent).
The thresholds indicated under Related substances
(Table 2034.-1) in the general monograph Substances for
pharmaceutical use (2034) do not apply.
Dextrin. To 1 g of the finely powdered substance to be
examined add 20 mL of ethanol (96 per cent) R and heat under
a reflux condenser. The substance dissolves completely.
Soluble starch, sulfite: maximum 15 ppm.
Dissolve 6.7 g in 15.0 mL of water R, heating on a water-bath.
Allow to cool and add 25 μL of iodine solution R5. The
solution is yellow.
Water (2.5.12): maximum 1.0 per cent, determined on 0.50 g.
◊Pyrogens (2.6.8). If intended for use in the manufacture
of large-volume parental preparations without a further
appropriate procedure for the removal of pyrogens, the
competent authority may require that it comply with the test
for pyrogens. Inject per kilogram of the rabbit’s mass 10 mL
of a solution in water for injections R containing 50 mg of the
substance to be examined per millilitre.◊
ASSAY
Liquid chromatography (2.2.29) as described in the test for
related substances with the following modification.
Injection: test solution and reference solution (a).
Calculate the percentage content of C6H12O6 taking into
account the assigned content of glucose monohydrate CRS.
IMPURITIES
Specified impurities: A, B, C, D.
A. 4-O-α-D-glucopyranosyl-D-glucopyranose (maltose),
B. 6-O-α-D-glucopyranosyl-D-glucopyranose (isomaltose),
C. α-D-glucopyranosyl-(1→4)-α-D-glucopyranosyl-(1→4)-Dglucopyranose
(maltotriose),
D. D-arabino-hex-2-ulopyranose (fructose).
01/2016:0178
corrected 9.1
GLUCOSE MONOHYDRATE(2)
Glucosum monohydricum
C6H12O6,H2O Mr 198.2
[77938-63-7]
DEFINITION
D-Glucopyranose monohydrate.
It is derived from starch.
Content: 97.5 per cent to 102.0 per cent (anhydrous substance).
CHARACTERS
Appearance: white or almost white, crystalline powder.
Solubility: freely soluble in water, very slightly soluble in
ethanol (96 per cent).
IDENTIFICATION
First identification: ◊A◊, B, E.
◊Second identification: C, D.◊
◊A. Specific optical rotation (2.2.7): + 52.5 to + 53.3
(anhydrous substance).
Dissolve 10.0 g in 80 mL of water R, add 0.2 mL of dilute
ammonia R1, allow to stand for 30 min and dilute to
100.0 mL with water R.◊
B. Examine the chromatograms obtained in the assay.
(2) This monograph has undergone pharmacopoeial harmonisation. See chapter 5.8 Pharmacopoeial harmonisation.
4168 See the information section on general monographs (cover pages)
EUROPEAN PHARMACOPOEIA 9.1 Glucose monohydrate
Results: the principal peak in the chromatogram obtained
with the test solution is similar in retention time and size
to the principal peak in the chromatogram obtained with
reference solution (a).
◊C. Thin-layer chromatography (2.2.27).
Solvent mixture: water R, methanol R (2:3 V/V).
Test solution. Dissolve 10 mg of the substance to be
examined in the solvent mixture and dilute to 20 mL with
the solvent mixture.
Reference solution (a). Dissolve 10 mg of glucose
monohydrate CRS in the solvent mixture and dilute to
20 mL with the solvent mixture.
Reference solution (b). Dissolve 10 mg each of fructose R,
glucose R, lactose monohydrate R and sucrose R in the
solvent mixture and dilute to 20 mL with the solvent
mixture.
Plate: TLC silica gel plate R.
Mobile phase: water R, methanol R, anhydrous acetic acid R,
ethylene chloride R (10:15:25:50 V/V/V/V); measure the
volumes accurately since a slight excess of water produces
cloudiness.
Application: 2 μL; thoroughly dry the points of application.
Development A: over 3/4 of the plate.
Drying A: in a current of warm air.
Development B: immediately, over 3/4 of the plate, after
renewing the mobile phase.
Drying B: in a current of warm air.
Detection: treat with a solution of 0.5 g of thymol R in a
mixture of 5 mL of sulfuric acid R and 95 mL of ethanol
(96 per cent) R; heat at 130 °C for 10 min.
System suitability: reference solution (b):
– the chromatogram shows 4 clearly separated spots.
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).
D. Dissolve 0.1 g in 10 mL of water R. Add 3 mL of
cupri-tartaric solution R and heat. A red precipitate is
formed.◊
E. Water (see Tests).
TESTS
Appearance of solution. The solution is clear (2.2.1) and not
more intensely coloured than reference solution BY7 (2.2.2,
Method II).
Dissolve 10.0 g in 15 mL of water R.
Conductivity (2.2.38): maximum 20 μS·cm−1
.
Dissolve 20.0 g in carbon dioxide-free water R prepared from
distilled water R and dilute to 100.0 mL with the same solvent.
Measure the conductivity of the solution while gently stirring
with a magnetic stirrer.
Related substances. Liquid chromatography (2.2.29).
Test solution. Dissolve 0.330 g of the substance to be examined
in water R and dilute to 10.0 mL with the same solvent.
Reference solution (a). Dissolve 0.330 g of glucose
monohydrate CRS in water R and dilute to 10.0 mL with the
same solvent.
Reference solution (b). Dilute 1.0 mL of the test solution to
250.0 mL with water R.
Reference solution (c). Dilute 25.0 mL of reference solution (b)
to 200.0 mL with water R.
Reference solution (d). Dissolve 5 mg of fructose R
(impurity D), 5 mg of maltose monohydrate R (impurity A)
and 5 mg of maltotriose R (impurity C) in water R and dilute
to 50 mL with the same solvent.
Column:
– size: l = 0.3 m, Ø = 7.8 mm;
– stationary phase: strong cation-exchange resin (calcium
form) R (9 μm);
– temperature: 85 ± 1 °C.
Mobile phase: degassed water R.
Flow rate: 0.3 mL/min.
Detection: refractometer maintained at a constant temperature
(40 °C for example).
Injection: 20 μL of the test solution and reference solutions (b),
(c) and (d).
Run time: 1.5 times the retention time of glucose.
Relative retention with reference to glucose (retention
time = about 21 min): impurity C = about 0.7; impurities A
and B = about 0.8; impurity D = about 1.3.
System suitability: reference solution (d):
– resolution: minimum 1.3 between the peaks due to
impurities C and A.
Limits:
– sum of impurities A and B: not more than the area of
the principal peak in the chromatogram obtained with
reference solution (b) (0.4 per cent);
– impurity C: not more than 0.5 times the area of the
principal peak in the chromatogram obtained with
reference solution (b) (0.2 per cent);
– impurity D: not more than 3 times the area of the principal
peak in the chromatogram obtained with reference
solution (c) (0.15 per cent);
– unspecified impurities: for each impurity, not more than
twice the area of the principal peak in the chromatogram
obtained with reference solution (c) (0.10 per cent);
– total: not more than 1.25 times the area of the principal
peak in the chromatogram obtained with reference
solution (b) (0.5 per cent);
– disregard limit: the area of the principal peak in the
chromatogram obtained with reference solution (c)
(0.05 per cent).
The thresholds indicated under Related substances
(Table 2034.-1) in the general monograph Substances for
pharmaceutical use (2034) do not apply.
Dextrin. To 1 g of the finely powdered substance to be
examined add 20 mL of ethanol (96 per cent) R and heat under
a reflux condenser. The substance dissolves completely.
Soluble starch, sulfite: maximum 15 ppm.
Dissolve 7.4 g in 15.0 mL of water R, heating on a water-bath.
Allow to cool and add 25 μL of iodine solution R5. The
solution is yellow.
Water (2.5.12): 7.5 per cent to 9.5 per cent, determined on
0.25 g.
◊Pyrogens (2.6.8). If intended for use in the manufacture
of large-volume parenteral preparations without a further
appropriate procedure for the removal of pyrogens, the
competent authority may require that it comply with the test
for pyrogens. Inject per kilogram of the rabbit’s mass 10 mL
of a solution in water for injections R containing 50 mg of the
substance to be examined per millilitre.◊
ASSAY
Liquid chromatography (2.2.29) as described in the test for
related substances with the following modification.
Injection: test solution and reference solution (a).
Calculate the percentage content of C6H12O6 taking into
account the assigned content of glucose monohydrate CRS.
General Notices (1) apply to all monographs and other texts 4169
Glucose monohydrate EUROPEAN PHARMACOPOEIA 9.1
IMPURITIES
Specified impurities: A, B, C, D.
A. 4-O-α-D-glucopyranosyl-D-glucopyranose (maltose),
B. 6-O-α-D-glucopyranosyl-D-glucopyranose (isomaltose),
C. α-D-glucopyranosyl-(1→4)-α-D-glucopyranosyl-(1→4)-Dglucopyranose
(maltotriose),
D. D-arabino-hex-2-ulopyranose (fructose).
4170 See the information section on general monographs (cover pages)