EUROPEAN PHARMACOPOEIA 6.

0 Sorbitol

STORAGE Detection : spray with 4-aminobenzoic acid solution R ;

Protected from light. dry in a current of cold air until the acetone is removed ;
heat at 100 °C for 15 min ; allow to cool and spray with
LABELLING a 2 g/l solution of sodium periodate R ; dry in a current
The label states the origin of the oleic acid used (animal or of cold air ; heat at 100 °C for 15 min.
vegetable). System suitability : reference solution (b) :
— the chromatogram shows 2 clearly separated spots.
Results : the principal spot in the chromatogram obtained
01/2008:0435 with the test solution is similar in position, colour and
size to the principal spot in the chromatogram obtained
with reference solution (a).
SORBITOL D. Specific optical rotation (2.2.7) : + 4.0 to + 7.0 (anhydrous
substance).
Sorbitolum Dissolve 5.00 g of the substance to be examined and 6.4 g
of disodium tetraborate R in 40 ml of water R. Allow to
stand for 1 h, shaking occasionally, and dilute to 50.0 ml
with water R. Filter if necessary.
TESTS
Appearance of solution. The solution is clear (2.2.1) and
colourless (2.2.2, Method II).
C6H14O6 Mr 182.2 Dissolve 5 g in water R and dilute to 50 ml with the same
DEFINITION solvent.
D-Glucitol (D-sorbitol). Conductivity (2.2.38) : maximum 20 µS·cm− 1.
Content : 97.0 per cent to 102.0 per cent (anhydrous Dissolve 20.0 g in carbon dioxide-free water R prepared
substance). from distilled water R and dilute to 100.0 ml with the same
solvent. Measure the conductivity of the solution while
CHARACTERS gently stirring with a magnetic stirrer.
Appearance : white or almost white, crystalline powder. Reducing sugars : maximum 0.2 per cent, expressed as
Solubility : very soluble in water, practically insoluble in glucose equivalent.
ethanol (96 per cent). Dissolve 5.0 g in 6 ml of water R with the aid of gentle
It shows polymorphism (5.9). heat. Cool and add 20 ml of cupri-citric solution R and a
few glass beads. Heat so that boiling begins after 4 min and
IDENTIFICATION maintain boiling for 3 min. Cool rapidly and add 100 ml
First identification : A. of a 2.4 per cent V/V solution of glacial acetic acid R and
Second identification : B, C, D. 20.0 ml of 0.025 M iodine. With continuous shaking, add
25 ml of a mixture of 6 volumes of hydrochloric acid R
A. Examine the chromatograms obtained in the assay. and 94 volumes of water R and, when the precipitate has
Results : the principal peak in the chromatogram obtained dissolved, titrate the excess of iodine with 0.05 M sodium
with the test solution is similar in retention time and size thiosulphate using 1 ml of starch solution R, added towards
to the principal peak in the chromatogram obtained with the end of the titration, as indicator. Not less than 12.8 ml of
reference solution (a). 0.05 M sodium thiosulphate is required.
B. Dissolve 0.5 g with heating in a mixture of 0.5 ml of Related products. Liquid chromatography (2.2.29).
pyridine R and 5 ml of acetic anhydride R. After 10 min, Test solution. Dissolve 5.0 g of the substance to be examined
pour the solution into 25 ml of water R and allow to in 20 ml of water R and dilute to 100.0 ml with the same
stand in iced water for 2 h. The precipitate, recrystallised solvent.
from a small volume of ethanol (96 per cent) R and dried
in vacuo, melts (2.2.14) at 98 °C to 104 °C. Reference solution (a). Dissolve 0.50 g of sorbitol CRS in
2 ml of water R and dilute to 10.0 ml with the same solvent.
C. Thin-layer chromatography (2.2.27).
Reference solution (b). Dilute 2.0 ml of the test solution to
Test solution. Dissolve 25 mg of the substance to be 100.0 ml with water R.
examined in water R and dilute to 10 ml with the same
solvent. Reference solution (c). Dilute 5.0 ml of reference solution (b)
to 100.0 ml with water R.
Reference solution (a). Dissolve 25 mg of sorbitol CRS in
water R and dilute to 10 ml with the same solvent. Reference solution (d). Dissolve 0.5 g of sorbitol R and 0.5 g
of mannitol R (impurity A) in 5 ml of water R and dilute to
Reference solution (b). Dissolve 25 mg of mannitol CRS
10.0 ml with the same solvent.
and 25 mg of sorbitol CRS in water R and dilute to 10 ml
with the same solvent. Column :
Plate : TLC silica gel G plate R. — size : l = 0.3 m, Ø = 7.8 mm ;
Mobile phase : water R, ethyl acetate R, propanol R — stationary phase : strong cation exchange resin (calcium
(10:20:70 V/V/V). form) R (9 µm) ;
Application : 2 µl. — temperature : 85 ± 1 °C.
Development : over a path of 17 cm. Mobile phase : degassed water R.
Drying : in air. Flow rate : 0.5 ml/min.

General Notices (1) apply to all monographs and other texts 2941
Sorbitol, liquid (crystallising) EUROPEAN PHARMACOPOEIA 6.0

Detection : refractometer maintained at a constant 01/2008:0436

temperature.
Injection : 20 µl of the test solution and reference SORBITOL, LIQUID (CRYSTALLISING)
solutions (b), (c) and (d).
Run time : 3 times the retention time of sorbitol.
Sorbitolum liquidum cristallisabile
Relative retention with reference to sorbitol (retention
time = about 27 min) : impurity C = about 0.6 ; DEFINITION
impurity A = about 0.8 ; impurity B = about 1.1. Aqueous solution of a hydrogenated, partly hydrolysed
System suitability : reference solution (d) : starch.
— resolution : minimum 2 between the peaks due to Content :
impurity A and sorbitol.
— anhydrous substance : 68.0 per cent m/m to 72.0 per
Limits : cent m/m,
— any impurity : for each impurity, not more than the area — D-glucitol (D-sorbitol, C6H14O6) : 92.0 per cent to 101.0 per
of the principal peak in the chromatogram obtained with cent (anhydrous substance).
reference solution (b) (2 per cent) ;
— total: not more than 1.5 times the area of the principal CHARACTERS
peak in the chromatogram obtained with reference Appearance : clear, colourless, syrupy liquid, miscible with
solution (b) (3 per cent) ; water.
— disregard limit : the area of the principal peak in the
chromatogram obtained with reference solution (c) IDENTIFICATION
(0.1 per cent). A. Examine the chromatograms obtained in the assay.
Lead (2.4.10) : maximum 0.5 ppm. Results : the principal peak in the chromatogram obtained
Nickel (2.4.15) : maximum 1 ppm. with the test solution is similar in retention time to
the principal peak in the chromatogram obtained with
Dissolve the substance to be examined in 150.0 ml of the
reference solution (a).
prescribed mixture of solvents.
B. To 7.0 g add 40 ml of water R and 6.4 g of disodium
Water (2.5.12) : maximum 1.5 per cent, determined on 1.00 g.
tetraborate R, allow to stand for 1 h, shaking occasionally,
Microbial contamination. If intended for use in the and dilute to 50.0 ml with water R. Filter if necessary.
manufacture of parenteral dosage forms, the total viable The angle of rotation (2.2.7) is 0° to + 1.5°.
aerobic count (2.6.12) is not more than 102 bacteria and C. It is a clear, syrupy liquid at a temperature of 25 °C.
102 fungi per gram, determined by plate count. It complies
with the tests for Escherichia coli and Salmonella (2.6.13). TESTS
Bacterial endotoxins (2.6.14) : less than 4 IU/g for Appearance of solution. The solution is clear (2.2.1) and
parenteral dosage forms having a concentration of less than colourless (2.2.2, Method II).
100 g/l of sorbitol, and less than 2.5 IU/g for parenteral
dosage forms having a concentration of 100 g/l or more of Dilute 7.0 g to 50 ml with water R.
sorbitol, if intended for use in the manufacture of parenteralConductivity (2.2.38) : maximum 10 µS·cm–1 measured on
dosage forms without a further appropriate procedure for the undiluted liquid sorbitol (crystallising) while gently
the removal of bacterial endotoxins. stirring with a magnetic stirrer.
ASSAY Reducing sugars : maximum 0.2 per cent calculated as
glucose equivalent.
Liquid chromatography (2.2.29) as described in the test for
related products with the following modification. To 5.0 g add 6 ml of water R, 20 ml of cupri-citric solution R
and a few glass beads. Heat so that boiling begins after
Injection : test solution and reference solution (a).
4 min and maintain boiling for 3 min. Cool rapidly and add
Calculate the percentage content of D-sorbitol from the 100 ml of a 2.4 per cent V/V solution of glacial acetic acid R
declared content of sorbitol CRS. and 20.0 ml of 0.025 M iodine. With continuous shaking,
LABELLING add 25 ml of a mixture of 6 volumes of hydrochloric acid R
and 94 volumes of water R and, when the precipitate has
The label states : dissolved, titrate the excess of iodine with 0.05 M sodium
— where applicable, the maximum concentration of bacterial thiosulphate using 1 ml of starch solution R, added towards
endotoxins ; the end of the titration, as indicator. Not less than 12.8 ml of
— where applicable, that the substance is suitable for use in 0.05 M sodium thiosulphate is required.
the manufacture of parenteral dosage forms. Lead (2.4.10) : maximum 0.5 ppm.
IMPURITIES Nickel (2.4.15) : maximum 1 ppm.
A. mannitol, Water (2.5.12) : 28.0 per cent to 32.0 per cent m/m,
determined on 0.1 g.
ASSAY
Liquid chromatography (2.2.29).
Test solution. Mix 1.00 g of the substance to be examined
with 20 ml of water R and dilute to 50.0 ml with the same
solvent.
B. iditol,
Reference solution (a). Dissolve 65.0 mg of sorbitol CRS in
C. maltitol. 2 ml of water R and dilute to 5.0 ml with the same solvent.

2942 See the information section on general monographs (cover pages)