EUROPEAN PHARMACOPOEIA 11.

0 Xylitol

STORAGE
In an airtight container, protected from light.
IMPURITIES
Specified impurities : A.
Other detectable impurities (the following substances would,
if present at a sufficient level, be detected by one or other of
the tests in the monograph. They are limited by the general
acceptance criterion for other/unspecified impurities and/or
by the general monograph Substances for pharmaceutical use
(2034). It is therefore not necessary to identify these impurities
for demonstration of compliance. See also 5.10. Control of
impurities in substances for pharmaceutical use) : B, C, D.
A. 2,6-dimethylaniline (2,6-xylidine),
B. N,N′-bis(2,6-dimethylphenyl)thiourea,
C. 1-isothiocyanato-2,6-dimethylbenzene,
D. N-(2,6-dimethylphenyl)-N′-(3-hydroxypropyl)thiourea.
07/2016:1381
corrected 10.0
XYLITOL
Xylitolum
C5H12O5 Mr 152.1
[87-99-0]
DEFINITION
Meso-xylitol.
Content : 98.0 per cent to 102.0 per cent (anhydrous substance).
CHARACTERS
Appearance : white or almost white, crystalline powder or
crystals.
Solubility : very soluble in water, sparingly soluble in ethanol
(96 per cent).
IDENTIFICATION
First identification : B.
Second identification : A, C.
A. Melting point (2.2.14): 92 °C to 96 °C.
B. Infrared absorption spectrophotometry (2.2.24).
Preparation : mulls in liquid paraffin R.
Comparison : xylitol CRS.
C. Thin-layer chromatography (2.2.27).
Test solution. Dissolve 25 mg of the substance to be
examined in water R and dilute to 10 mL with the same
solvent.
Reference solution (a). Dissolve 25 mg of xylitol CRS in
water R and dilute to 10 mL with the same solvent.
Reference solution (b). Dissolve 25 mg of mannitol R and
25 mg of xylitol R in water R and dilute to 10 mL with the
same solvent.
Plate : TLC silica gel plate R.
Mobile phase : water R, ethyl acetate R, propanol R
(10:20:70 V/V/V).
Application : 2 μL.
Development : over 3/4 of the plate.
Drying : in air.
Detection : spray with 4-aminobenzoic acid solution R, dry
in a current of cold air until the acetone is removed, then
heat at 100 °C for 15 min ; allow to cool, spray with a 2 g/L
solution of sodium periodate R, dry in a current of cold air,
then heat at 100 °C for 15 min.
System suitability : reference solution (b) :
– the chromatogram shows 2 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).
TESTS
Appearance of solution. The solution is not more opalescent
than reference suspension IV (2.2.1) and not more intensely
coloured than reference solution BY7 (2.2.2, Method II).
Dissolve 2.5 g in water R and dilute to 50.0 mL with the same
solvent.
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.
Reducing sugars : maximum 0.2 per cent, calculated as
glucose equivalent.
Dissolve 5.0 g in 6 mL of water R with the aid of gentle 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 maintain
boiling for 3 min. Cool rapidly and add 100 mL of a 2.4 per
cent V/V solution of glacial acetic acid R and 20.0 mL of
0.025 M iodine. With continuous shaking, add 25 mL of a
mixture of 6 volumes of hydrochloric acid R and 94 volumes
of water R and, when the precipitate has dissolved, titrate the
excess of iodine with 0.05 M sodium thiosulfate using 1 mL of
starch solution R, added towards the end of the titration, as
indicator. Not less than 12.8 mL of 0.05 M sodium thiosulfate
is required.
Related substances. Gas chromatography (2.2.28).
Internal standard solution. Dissolve 5 mg of erythritol R in
water R and dilute to 25.0 mL with the same solvent.
Test solution (a). Dissolve 5.000 g of the substance to be
examined in water R and dilute to 100.0 mL with the same
solvent.
Test solution (b). Dilute 1.0 mL of test solution (a) to 10.0 mL
with water R.

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Xylitol EUROPEAN PHARMACOPOEIA 11.0

Reference solution (a). Dissolve 5.0 mg each of L-arabinitol CRS Lead (2.4.10) : maximum 0.5 ppm.
(impurity A), galactitol CRS (impurity B), mannitol CRS Dissolve the substance to be examined in 150.0 mL of the
(impurity C) and sorbitol CRS (impurity D) in water R and prescribed mixture of solvents.
dilute to 20.0 mL with the same solvent.
Nickel (2.4.15): maximum 1 ppm.
Reference solution (b). Dissolve 50.0 mg of xylitol CRS in
water R and dilute to 10.0 mL with the same solvent. Dissolve the substance to be examined in 150.0 mL of the
prescribed mixture of solvents.
Pipette 1.0 mL of test solutions (a) and (b) and reference
solutions (a) and (b) into 4 separate 100 mL round-bottomed Water (2.5.12) : maximum 1.0 per cent, determined on 1.00 g.
flasks. Add 1.0 mL of the internal standard solution to each of Bacterial endotoxins (2.6.14) : less than 4 IU/g if the
the flasks containing test solution (a) or reference solution (a), concentration is less than 100 g/L of xylitol and less than
and 5.0 mL of the internal standard solution to each of the 2.5 IU/g if the concentration is 100 g/L or more of xylitol,
flasks containing test solution (b) or reference solution (b). when intended for use in the manufacture of parenteral
Evaporate each mixture to dryness in a water-bath at 60 °C preparations without a further appropriate procedure for the
by suitable means. Dissolve each dry residue in 1 mL of removal of bacterial endotoxins.
anhydrous pyridine R, add 1 mL of acetic anhydride R to each
flask and boil each solution under reflux for 1 h to complete ASSAY
acetylation. Gas chromatography (2.2.28) as described in the test for
Column : related substances with the following modifications.
– size : l = 30 m, Ø = 0.25 mm ; Injection : 1 μL of test solution (b) and reference solution (b)
– stationary phase : cyanopropyl(7)phenyl(7)methyl(86)poly- (solutions obtained after derivatisation).
siloxane R (0.25 μm). Calculate the percentage content of C5H12O5 using the
Carrier gas : nitrogen R. following expression :
Flow rate : 1 mL/min. mt R v
Split ratio : 1:50 to 1:100. T´ ´
mv R t
Temperature :
Time Temperature
T = declared percentage content of xylitol CRS ;
(min) (°C) mt = mass of xylitol CRS in 1 mL of reference
Column 0-1 170 solution (b), in milligrams ;
1-6 170 → 230 mv = mass of the substance to be examined in 1 mL of
test solution (b), in milligrams ;
6 - 30 230
Rt = ratio of the area of the peak due to derivatised
Injection port 250 xylitol to the area of the peak due to the derivatised
Detector 250 internal standard in the chromatogram obtained
with reference solution (b) ;
Detection : flame ionisation. Rv = ratio of the area of the peak due to derivatised
Injection : 1 μL of test solution (a) and reference solution (a) xylitol to the area of the peak due to the derivatised
(solutions obtained after derivatisation). internal standard in the chromatogram obtained
Relative retention with reference to xylitol (retention with test solution (b).
time = about 15 min) : internal standard = about 0.6 ;
impurity A = about 0.9 ; impurity C = about 1.4 ; LABELLING
impurity B = about 1.45 ; impurity D = about 1.5. The label states :
System suitability : reference solution (a) : – where applicable, the maximum concentration of bacterial
– resolution : minimum 2.0 between the peaks due to endotoxins ;
impurities B and D. – where applicable, that the substance is suitable for use in
Calculate the percentage content of each related substance in the manufacture of parenteral preparations.
the substance to be examined using the following expression :
IMPURITIES
m R
100 ´ s ´ u
mu R s
ms = mass of the particular component in 1 mL of
reference solution (a), in milligrams ;
mu = mass of the substance to be examined in 1 mL of A. L-arabinitol,
test solution (a), in milligrams ;
Rs = ratio of the area of the peak due to the particular
derivatised component to the area of the peak
due to the derivatised internal standard in
the chromatogram obtained with reference
solution (a) ;
Ru = ratio of the area of the peak due to the particular B. meso-galactitol,
derivatised component to the area of the peak
due to the derivatised internal standard in the
chromatogram obtained with test solution (a).
The sum of the percentage contents of the related substances
in the chromatogram obtained with test solution (a) is not
greater than 2.0 per cent. Disregard any peak with an area
corresponding to a percentage content of 0.05 per cent or less. C. D-mannitol,

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EUROPEAN PHARMACOPOEIA 11.0 Xylometazoline hydrochloride

is removed and an area of the coating below the points

of application does not give a blue colour with a drop of
potassium iodide and starch solution R.
Detection : spray with potassium iodide and starch
solution R.
D. D-glucitol (D-sorbitol). 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
the reference solution.
01/2008:1162 C. Dissolve about 0.5 mg in 1 mL of methanol R. Add
corrected 10.1 0.5 mL of a freshly prepared 50 g/L solution of sodium
nitroprusside R and 0.5 mL of a 20 g/L solution of
sodium hydroxide R. Allow to stand for 10 min and add
1 mL of an 80 g/L solution of sodium hydrogen carbonate R.
A violet colour develops.
XYLOMETAZOLINE D. Dissolve 0.2 g in 1 mL of water R, add 2.5 mL of ethanol
(96 per cent) R and 2 mL of 1 M sodium hydroxide. Mix
HYDROCHLORIDE thoroughly and examine in ultraviolet light at 365 nm.
The solution shows no fluorescence or at most the
Xylometazolini hydrochloridum same fluorescence as a blank solution prepared in the
same manner. The identification is not valid unless a
solution prepared in the same manner using naphazoline
hydrochloride CRS instead of the substance to be examined
shows a distinct bluish fluorescence.
E. It gives reaction (a) of chlorides (2.3.1).

C16H25ClN2 Mr 280.8 Appearance of solution. The solution is clear (2.2.1) and not
[1218-35-5]
DEFINITION
2-[4-(1,1-Dimethylethyl)-2,6-dimethylbenzyl]-4,5-dihydro-
1H-imidazole hydrochloride.
Content : 99.0 per cent to 101.0 per cent (dried substance).
CHARACTERS
Appearance : white or almost white, crystalline powder.
Solubility : freely soluble in water, in ethanol (96 per cent) and indicator to yellow.
in methanol.
IDENTIFICATION
First identification : A, E.
Second identification : B, C, D, E.
A. Infrared absorption spectrophotometry (2.2.24).
Comparison : xylometazoline hydrochloride CRS.
B. Thin-layer chromatography (2.2.27).
Test solution. Dissolve 20 mg of the substance to be
examined in methanol R and dilute to 5 mL with the same
solvent.
Reference solution. Dissolve 20 mg of xylometazoline
hydrochloride CRS in methanol R and dilute to 5 mL with
the same solvent.
Plate : TLC silica gel G plate R.
Mobile phase : concentrated ammonia R, methanol R
(5:100 V/V).
Application : 5 μL.
Development : over 2/3 of the plate.
Drying : in air.
Chlorine treatment : at the bottom of a chromatographic
tank place a beaker containing a mixture of 1 volume of
hydrochloric acid R1, 1 volume of water R and 2 volumes of
a 15 g/L solution of potassium permanganate R. Close the
tank and allow to stand for 15 min. Place the dried plate in
the tank and reclose the tank. Leave the plate in contact
with the chlorine vapour for 5 min. Withdraw the plate and
place it in a current of cold air until the excess of chlorine
TESTS
more intensely coloured than reference solution Y6 (2.2.2,
Method II).
Dissolve 2.5 g in water R and dilute to 50.0 mL with the same
solvent.
Acidity or alkalinity. Dissolve 0.25 g in carbon dioxide-free
water R and dilute to 25 mL with the same solvent. Add 0.1 mL
of methyl red solution R and 0.1 mL of 0.01 M hydrochloric
acid. The solution is red. Not more than 0.2 mL of 0.01 M
sodium hydroxide is required to change the colour of the
Related substances. Liquid chromatography (2.2.29).
Test solution. Dissolve 50.0 mg of the substance to be
examined in water R and dilute to 50.0 mL with the same
solvent. Allow to stand for 1 h before injection.
Reference solution (a). Dilute 5.0 mL of the test solution to
100.0 mL with water R. Dilute 2.0 mL of this solution to
100.0 mL with water R.
Reference solution (b). Dissolve 5.0 mg of xylometazoline
impurity A CRS and 5 mg of the substance to be examined in
water R and dilute to 50.0 mL with the same solvent. Dilute
10.0 mL of this solution to 50.0 mL with water R.
Reference solution (c). Dilute 5.0 mL of reference solution (b)
to 50.0 mL with water R.
Column :
– size : l = 0.25 m, Ø = 4.6 mm ;
– stationary phase : end-capped octadecylsilyl silica gel for
chromatography with embedded polar groups R (5 μm).
Mobile phase :
– mobile phase A : 1.36 g/L solution of potassium dihydrogen
phosphate R adjusted to pH 3.0 with phosphoric acid R ;
– mobile phase B : acetonitrile for chromatography R ;
Time Mobile phase A Mobile phase B
(min) (per cent V/V) (per cent V/V)
0-5 70 30
5 - 20 70 → 15 30 → 85
20 - 35 15 85

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