EUROPEAN PHARMACOPOEIA 7.

0 Xanthan gum

04/2009:1277 Temperature :
— column : 165 °C ;
XANTHAN GUM — injection port and detector : 200 °C.
Detection : flame ionisation.
Xanthani gummi Injection : 5 μL.
Relative retention with reference to 2-propanol :
[11138-66-2] 2-methyl-2-propanol = about 1.5.
Limit :
DEFINITION — 2-propanol : maximum 750 ppm.
High-molecular-mass anionic polysaccharide produced Other polysaccharides. Thin-layer chromatography (2.2.27).
by fermentation of carbohydrates with Xanthomonas
campestris. It consists of a principal chain of β(1→4)-linked Test solution. To 10 mg of the substance to be examined in
D-glucose units with trisaccharide side chains, on alternating
a thick-walled centrifuge test tube add 2 mL of a 230 g/L
anhydroglucose units, consisting of 1 glucuronic acid unit solution of trifluoroacetic acid R, shake vigorously to dissolve
included between 2 mannose units. Most of the terminal units the forming gel, stopper the test tube, and heat the mixture at
contain a pyruvate moiety and the mannose unit adjacent to the 120 °C for 1 h. Centrifuge the hydrolysate, transfer the clear
principal chain may be acetylated at C-6. supernatant liquid carefully into a 50 mL flask, add 10 mL of
water R and evaporate the solution to dryness under reduced
Xanthan gum has a relative molecular mass of approximately pressure. Take up the residue thus obtained in 10 mL of water R
6
1 × 10 . It exists as the sodium, potassium or calcium salt. and evaporate to dryness under reduced pressure. Wash 3 times
Content : minimum 1.5 per cent of pyruvoyl groups (C3H3O2 ; with 20 mL of methanol R and evaporate under reduced
Mr 71.1) (dried substance). pressure. To the resulting clear film which has no odour of
acetic acid, add 0.1 mL of water R and 1 mL of methanol R.
CHARACTERS Centrifuge to separate the amorphous precipitate. Dilute the
Appearance : white or yellowish-white, free-flowing powder. supernatant liquid, if necessary, to 1 mL with methanol R.
Solubility : soluble in water giving a highly viscous solution, Reference solution. Dissolve 10 mg of glucose R and 10 mg
practically insoluble in organic solvents. of mannose R in 2 mL of water R and dilute to 10 mL with
methanol R.
IDENTIFICATION Plate : TLC silica gel plate R.
A. In a flask, suspend 1 g in 15 mL of 0.1 M hydrochloric acid. Mobile phase : 16 g/L solution of sodium dihydrogen
Close the flask with a fermentation bulb containing barium phosphate R, butanol R, acetone R (10:40:50 V/V/V).
hydroxide solution R and heat carefully for 5 min. The Application : 5 μL as bands.
barium hydroxide solution shows a white turbidity.
Development : over a path of 15 cm.
B. To 300 mL of water R, previously heated to 80 °C and stirred Detection : spray with a solution of 0.5 g of diphenylamine R
rapidly with a mechanical stirrer in a 400 mL beaker, add, at in 25 mL of methanol R to which 0.5 mL of aniline R and
the point of maximum agitation, a dry blend of 1.5 g of carob 2.5 mL of phosphoric acid R have been added. Heat for 5 min
bean gum R and 1.5 g of the substance to be examined. Stir at 120 °C and examine in daylight.
until the mixture forms a solution, and then continue stirring
for 30 min or longer. Do not allow the water temperature to System suitability : reference solution:
drop below 60 °C during stirring. Discontinue stirring and — the chromatogram shows 2 clearly separated greyish-brown
allow the mixture to stand for at least 2 h. A firm rubbery zones due to glucose and mannose in the middle third.
gel forms after the temperature drops below 40 °C but no Results : the chromatogram obtained with the test solution
such gel forms in a 1 per cent control solution of the sample shows 2 zones corresponding to the zones due to glucose and
prepared in the same manner but omitting the carob bean mannose in the chromatogram obtained with the reference
gum. solution. In addition, 1 weak reddish and 2 faint bluish-grey
bands may be visible just above the line of application. 1 or 2
TESTS bluish-grey bands may also be seen in the upper quarter of the
pH (2.2.3) : 6.0 to 8.0 for a 10.0 g/L solution. chromatogram. No other bands are visible.
2-Propanol. Gas chromatography (2.2.28). Loss on drying (2.2.32) : maximum 15.0 per cent, determined
Internal standard solution. Dilute 0.50 g of 2-methyl-2- on 1.000 g by drying in an oven at 105 °C for 2.5 h.
propanol R to 500 mL with water R. Total ash (2.4.16) : 6.5 per cent to 16.0 per cent.
Test solution. To 200 mL of water R in a 1000 mL Microbial contamination
round-bottomed flask, add 5.0 g of the substance to be examined TAMC : acceptance criterion 103 CFU/g (2.6.12).
and 1 mL of a 10 g/L emulsion of dimeticone R in liquid TYMC : acceptance criterion 102 CFU/g (2.6.12).
paraffin R, stopper the flask and shake for 1 h. Distil about
90.0 mL, mix the distillate with 4.0 mL of the internal standard ASSAY
solution and dilute to 100.0 mL with water R. Test solution. Dissolve a quantity of the substance to be
Reference solution. Dilute a suitable quantity of 2-propanol R, examined corresponding to 120.0 mg of the dried substance in
accurately weighed, with water R to obtain a solution having water R and dilute to 20.0 mL with the same solvent.
a known concentration of 2-propanol of about 1 mg/mL. To Reference solution. Dissolve 45.0 mg of pyruvic acid R in
4.0 mL of this solution add 4.0 mL of the internal standard water R and dilute to 500.0 mL with the same solvent.
solution and dilute to 100.0 mL with water R.
Place 10.0 mL of the test solution in a 50 mL round-bottomed
Column : flask, add 20.0 mL of 0.1 M hydrochloric acid and weigh.
— size : l = 1.8 m, Ø = 4.0 mm ; Boil on a water-bath under a reflux condenser for 3 h.
— stationary phase : styrene-divinylbenzene copolymer R Weigh and adjust to the initial mass with water R. In a
(149-177 μm). separating funnel mix 2.0 mL of the solution with 1.0 mL of
dinitrophenylhydrazine-hydrochloric solution R. Allow to
Carrier gas : helium for chromatography R. stand for 5 min and add 5.0 mL of ethyl acetate R. Shake and
Flow rate: 30 mL/min. allow the solids to settle. Collect the upper layer and shake with

General Notices (1) apply to all monographs and other texts 3237
Xylazine hydrochloride for veterinary use EUROPEAN PHARMACOPOEIA 7.0

3 quantities, each of 5.0 mL, of sodium carbonate solution R. CHARACTERS

Combine the aqueous layers and dilute to 50.0 mL with sodium Appearance: white or almost white, crystalline powder,
carbonate solution R. Mix. Treat 10.0 mL of the reference hygroscopic.
solution at the same time and in the same manner as for the
test solution. Solubility : freely soluble in water, very soluble in methanol,
freely soluble in methylene chloride.
Immediately measure the absorbance (2.2.25) of the 2 solutions
at 375 nm, using sodium carbonate solution R as the IDENTIFICATION
compensation liquid.
A. Infrared absorption spectrophotometry (2.2.24).
The absorbance of the test solution is not less than that of the
reference solution, which corresponds to a content of pyruvoyl Comparison : xylazine hydrochloride CRS.
groups of not less than 1.5 per cent. B. It gives reaction (b) of chlorides (2.3.1).
FUNCTIONALITY-RELATED CHARACTERISTICS TESTS
This section provides information on characteristics that are
Solution S. Dissolve 5.0 g in carbon dioxide-free water R
recognised as being relevant control parameters for one or
prepared from distilled water R, heating at 60 °C if necessary ;
more functions of the substance when used as an excipient
allow to cool and dilute to 50.0 mL with the same solvent.
(see chapter 5.15). This section is a non-mandatory part of the
monograph and it is not necessary to verify the characteristics Appearance of solution. Solution S is not more opalescent
to demonstrate compliance. Control of these characteristics than reference suspension II (2.2.1) and is colourless (2.2.2,
can however contribute to the quality of a medicinal product Method II).
by improving the consistency of the manufacturing process pH (2.2.3) : 4.0 to 5.5 for solution S.
and the performance of the medicinal product during use.
Where control methods are cited, they are recognised as being Impurity A : maximum 100 ppm.
suitable for the purpose, but other methods can also be used. Solution A. Dissolve 0.25 g of the substance to be examined in
Wherever results for a particular characteristic are reported, methanol R and dilute to 10 mL with the same solvent. This
the control method must be indicated. solution is used to prepare the test solution.
The following characteristics may be relevant for xanthan Solution B. Dissolve 50 mg of 2,6-dimethylaniline R in
gum used as viscosity-increasing agent. methanol R and dilute to 100 mL with the same solvent. Dilute
Apparent viscosity (2.2.10) : typically minimum 600 mPa·s. 1 mL of the solution to 100 mL with methanol R. This solution
Add 3.0 g within 45-90 s into 250 mL of a 12 g/L solution is used to prepare the reference solution.
of potassium chloride R in a 500 mL beaker stirring with Using 2 flat-bottomed tubes with an inner diameter of about
a low-pitch propeller-type stirrer rotating at 800 r/min. 10 mm, place in the first tube 2 mL of solution A, and in the
When adding the substance take care that agglomerates are second tube 1 mL of solution B and 1 mL of methanol R. To
destroyed. Add an additional quantity of 44 mL of water R, to each tube add 1 mL of a freshly prepared 10 g/L solution of
rinse any adhering residue from the walls of the beaker. Stir dimethylaminobenzaldehyde R in methanol R and 2 mL of
the preparation at 800 r/min for 2 h whilst maintaining the glacial acetic acid R and allow to stand at room temperature
temperature at 24 ± 1 °C. Determine the viscosity within 15 min for 10 min. Compare the colours in diffused daylight, viewing
at 24 ± 1 °C using a rotating viscosimeter set at 60 r/min and vertically against a white background. Any yellow colour in
equipped with a rotating spindle 1.6 mm high and 12.7 mm in the test solution is not more intense than that in the reference
diameter which is attached to a shaft 3.2 mm in diameter. The solution.
distance from the top of the cylinder to the lower tip of the shaft
Related substances. Liquid chromatography (2.2.29). Prepare
should be 25.4 mm and the immersion depth 50.0 mm. the solutions immediately before use.
The following characteristics may be relevant for xanthan Solvent mixture. Mix 8 volumes of acetonitrile R, 30 volumes of
gum used as matrix former in prolonged-release tablets. methanol R and 62 volumes of a 2.72 g/L solution of potassium
Apparent viscosity : see test above. dihydrogen phosphate R adjusted to pH 7.2 with dilute sodium
Particle-size distribution (2.9.31 or 2.9.38). hydroxide solution R.
Powder flow (2.9.36). Test solution. Dissolve 0.100 g of the substance to be examined
in the solvent mixture and dilute to 20.0 mL with the solvent
mixture.
07/2010:1481 Reference solution (a). Dissolve 5.0 mg of the substance to
be examined, 5.0 mg of 2,6-dimethylaniline R (impurity A),
XYLAZINE HYDROCHLORIDE 5.0 mg of xylazine impurity C CRS and 5.0 mg of xylazine
impurity E CRS in acetonitrile R and dilute to 100.0 mL with
FOR VETERINARY USE the same solvent. Dilute 1.0 mL of this solution to 10.0 mL with
the solvent mixture.
Xylazini hydrochloridum ad usum Reference solution (b). With the aid of ultrasound, dissolve the
veterinarium contents of a vial of xylazine impurity mixture CRS (impurities
B and D) in 1.0 mL of the solvent mixture.
Column :
— size : l = 0.15 m, Ø = 3.9 mm ;
— stationary phase : end-capped octylsilyl silica gel for
chromatography with polar incorporated groups R (5 μm);
C12H17ClN2S Mr 256.8
— temperature : 40 °C.
[23076-35-9]
Mobile phase :
DEFINITION
— mobile phase A : mix 30 volumes of methanol R and
N-(2,6-Dimethylphenyl)-5,6-dihydro-4H-1,3-thiazin-2-amine 70 volumes of a 2.72 g/L solution of potassium dihydrogen
hydrochloride. phosphate R adjusted to pH 7.2 with dilute sodium
Content : 98.0 per cent to 102.0 per cent (dried substance). hydroxide solution R;

3238 See the information section on general monographs (cover pages)