EUROPEAN PHARMACOPOEIA 10.

0 Xanthan gum

07/2017:1277 Flow rate : 30 mL/min.

Temperature :
– column : 165 °C ;
– injection port and detector : 200 °C.
XANTHAN GUM Detection : flame ionisation.
Injection : 5 μL.
Xanthani gummi Relative retention with reference to 2-propanol :
2-methyl-2-propanol = about 1.5.
[11138-66-2] Limit :
– 2-propanol : maximum 750 ppm.
DEFINITION
High-molecular-mass anionic polysaccharide produced Loss on drying (2.2.32) : maximum 15.0 per cent, determined
by fermentation of carbohydrates with Xanthomonas on 1.000 g by drying in an oven at 105 °C for 2.5 h.
campestris. It consists of a principal chain of β(1→4)-linked Total ash (2.4.16) : 6.5 per cent to 16.0 per cent.
D-glucose units with trisaccharide side chains, on alternating
anhydroglucose units, consisting of 1 glucuronic acid unit ASSAY
included between 2 mannose units. Most of the terminal units Test solution. Dissolve a quantity of the substance to be
contain a pyruvate moiety and the mannose unit adjacent to examined corresponding to 120.0 mg of the dried substance
the principal chain may be acetylated at C-6. in water R and dilute to 20.0 mL with the same solvent.
Xanthan gum has a relative molecular mass of approximately Reference solution. Dissolve 45.0 mg of pyruvic acid R in
1 × 106. It exists as the sodium, potassium or calcium salt. water R and dilute to 500.0 mL with the same solvent.
Content : minimum 1.5 per cent of pyruvate acetal groups Place 10.0 mL of the test solution in a 50 mL round-bottomed
(C3H3O2 ; Mr 71.1) (dried substance). flask, add 20.0 mL of 0.1 M hydrochloric acid and weigh.
Boil on a water-bath under a reflux condenser for 3 h.
CHARACTERS Weigh and adjust to the initial mass with water R. In a
Appearance : white or yellowish-white, free-flowing powder. separating funnel mix 2.0 mL of the solution with 1.0 mL
Solubility : soluble in water giving a highly viscous solution, of dinitrophenylhydrazine-hydrochloric solution R. Allow to
practically insoluble in organic solvents. stand for 5 min and add 5.0 mL of ethyl acetate R. Shake
and allow the solids to settle. Collect the upper layer and
IDENTIFICATION shake with 3 quantities, each of 5.0 mL, of sodium carbonate
A. In a flask, suspend 1 g in 15 mL of 0.1 M hydrochloric acid. solution R. Combine the aqueous layers and dilute to 50.0 mL
Close the flask with a fermentation bulb containing barium with sodium carbonate solution R. Mix. Treat 10.0 mL of the
hydroxide solution R and heat carefully for 5 min. The reference solution at the same time and in the same manner
barium hydroxide solution shows a white turbidity. as for the test solution.
B. To 300 mL of water R, previously heated to 80 °C and Immediately measure the absorbance (2.2.25) of the
stirred rapidly with a mechanical stirrer in a 400 mL beaker, 2 solutions at 375 nm, using sodium carbonate solution R as
add, at the point of maximum agitation, a dry blend of the compensation liquid.
1.5 g of carob bean gum R and 1.5 g of the substance to The absorbance of the test solution is not less than that of the
be examined. Stir until the mixture forms a solution, and reference solution, which corresponds to a content of pyruvoyl
then continue stirring for 30 min or longer. Do not allow groups of not less than 1.5 per cent.
the water temperature to drop below 60 °C during stirring.
Discontinue stirring and allow the mixture to stand for at FUNCTIONALITY-RELATED CHARACTERISTICS
least 2 h. A firm rubbery gel forms after the temperature This section provides information on characteristics that are
drops below 40 °C but no such gel forms in a 1 per cent recognised as being relevant control parameters for one or
control solution of the sample prepared in the same manner more functions of the substance when used as an excipient
but omitting the carob bean gum. (see chapter 5.15). Some of the characteristics described in
the Functionality-related characteristics section may also be
TESTS present in the mandatory part of the monograph since they
pH (2.2.3) : 6.0 to 8.0 for a 10.0 g/L solution in carbon also represent mandatory quality criteria. In such cases, a
dioxide-free water R. cross-reference to the tests described in the mandatory part is
2-Propanol. Gas chromatography (2.2.28). included in the Functionality-related characteristics section.
Control of the characteristics can contribute to the quality
Internal standard solution. Dilute 0.50 g of 2-methyl-2-
of a medicinal product by improving the consistency of the
propanol R to 500 mL with water R.
manufacturing process and the performance of the medicinal
Test solution. To 200 mL of water R in a 1000 mL product during use. Where control methods are cited, they are
round-bottomed flask, add 5.0 g of the substance to be recognised as being suitable for the purpose, but other methods
examined and 1 mL of a 10 g/L emulsion of dimeticone R in can also be used. Wherever results for a particular characteristic
liquid paraffin R, stopper the flask and shake for 1 h. Distil are reported, the control method must be indicated.
about 90.0 mL, mix the distillate with 4.0 mL of the internal
The following characteristics may be relevant for xanthan gum
standard solution and dilute to 100.0 mL with water R.
used as viscosity-increasing agent.
Reference solution. Dilute a suitable quantity of 2-propanol R,
accurately weighed, with water R to obtain a solution having Viscosity (2.2.10) : typically minimum 600 mPa·s.
a known concentration of 2-propanol of about 1 mg/mL. To Add 3.0 g (dried substance) within 45-90 s into 250 mL of a
4.0 mL of this solution add 4.0 mL of the internal standard 12 g/L solution of potassium chloride R in a 500 mL beaker
solution and dilute to 100.0 mL with water R. stirring with a low-pitch propeller-type stirrer rotating
Column : at 800 r/min. When adding the substance take care that
agglomerates are destroyed. Add an additional quantity of
– size : l = 1.8 m, Ø = 4.0 mm ; 44 mL of water R, to rinse any adhering residue from the
– stationary phase : ethylvinylbenzene-divinylbenzene walls of the beaker. Stir the preparation at 800 r/min for 2 h
copolymer R (149-177 μm). whilst maintaining the temperature at 24 ± 1 °C. Determine
Carrier gas : helium for chromatography R. the viscosity within 15 min at 24 ± 1 °C using a rotating

General Notices (1) apply to all monographs and other texts 4221
Xylazine hydrochloride for veterinary use EUROPEAN PHARMACOPOEIA 10.0

Test solution. Dissolve 0.100 g of the substance to be examined

viscosimeter set at 60 r/min and equipped with a rotating
in the solvent mixture and dilute to 20.0 mL with the solvent
spindle 1.78 mm high and 12.60 mm in diameter which is
mixture.
attached to a shaft 3.2 mm in diameter. The distance from
the top of the cylinder to the lower tip of the shaft should be
Reference solution (a). Dilute 1.0 mL of the test solution
25.60 mm and the immersion depth 50.0 mm. to 50.0 mL with the solvent mixture. Dilute 1.0 mL of this
The following characteristics may be relevant for xanthan gum
solution to 10.0 mL with the solvent mixture.
used as matrix former in prolonged-release tablets.
Reference solution (b). Dissolve 5.0 mg of bupivacaine
Viscosity : see test above. impurity F CRS ( xylazine impurity A) in acetonitrile R and
Particle-size distribution (2.9.31 or 2.9.38). dilute to 100.0 mL with the same solvent.
Powder flow (2.9.36). Reference solution (c). Dilute 1.0 mL of reference solution (b)
to 100.0 mL with the solvent mixture.
Reference solution (d). Dilute 1 mL of the test solution to
07/2019:1481 100 mL with the solvent mixture. Mix 10 mL of this solution
with 10 mL of reference solution (b). Dilute 1 mL of this
solution to 5 mL with the solvent mixture.
Column :
– size : l = 0.15 m, Ø = 3.9 mm ;
XYLAZINE HYDROCHLORIDE – stationary phase : end-capped octylsilyl silica gel for
FOR VETERINARY USE chromatography with polar incorporated groups R (5 μm) ;
– temperature : 40 °C.
Xylazini hydrochloridum ad usum Mobile phase :
veterinarium – mobile phase A : mix 30 volumes of methanol R1 and
70 volumes of a 2.72 g/L solution of potassium dihydrogen
phosphate R previously adjusted to pH 7.2 with dilute
sodium hydroxide solution R ;
– mobile phase B : methanol R1, acetonitrile for
chromatography R (30:70 V/V) ;
C12H17ClN2S Mr 256.8 Time Mobile phase A Mobile phase B
[23076-35-9] (min) (per cent V/V) (per cent V/V)
0 - 15 89 → 28 11 → 72
DEFINITION
N-(2,6-Dimethylphenyl)-5,6-dihydro-4H-1,3-thiazin-2-amine 15 - 21 28 72
hydrochloride.
Flow rate : 1.0 mL/min.
Content : 98.0 per cent to 102.0 per cent (dried substance).
Detection : spectrophotometer at 230 nm.
CHARACTERS Injection : 20 μL of the test solution and reference solutions (a),
Appearance : white or almost white, crystalline powder, (c) and (d).
hygroscopic.
Identification of impurities: use the chromatogram obtained
Solubility : freely soluble in water, very soluble in methanol, with reference solution (c) to identify the peak due to
freely soluble in methylene chloride. impurity A.
It shows polymorphism (5.9). Relative retention with reference to xylazine (retention
IDENTIFICATION time = about 8 min) : impurity A = about 0.8.
A. Infrared absorption spectrophotometry (2.2.24). System suitability : reference solution (d) :
Comparison : xylazine hydrochloride CRS. – resolution : minimum 4.0 between the peaks due to
impurity A and xylazine.
If the spectra obtained show differences, dissolve the
substance to be examined and the reference substance Calculation of percentage contents :
separately in the minimum volume of water R, evaporate to – for impurity A, use the concentration of impurity A in
dryness at 60 °C at a pressure of 10-20 kPa, and record new reference solution (c);
spectra using the residues.
– for impurities other than A, use the concentration of
B. It gives reaction (b) of chlorides (2.3.1). xylazine hydrochloride in reference solution (a).
TESTS Limits :
Solution S. Dissolve 5.0 g in carbon dioxide-free water R, – impurity A : maximum 0.01 per cent ;
heating at 60 °C if necessary ; allow to cool and dilute to – unspecified impurities : for each impurity, maximum
50.0 mL with the same solvent. 0.20 per cent ;
Appearance of solution. Solution S is not more opalescent – total : maximum 0.2 per cent ;
than reference suspension II (2.2.1) and is colourless (2.2.2,
– reporting threshold : 0.10 per cent, except for impurity A.
Method II).
Heavy metals (2.4.8): maximum 10 ppm.
pH (2.2.3): 4.0 to 5.5 for solution S.
12 mL of solution S complies with test A. Prepare the reference
Related substances. Liquid chromatography (2.2.29). Prepare
solution using 10 mL of lead standard solution (1 ppm Pb) R.
the solutions immediately before use.
Solvent mixture. Mix 8 volumes of acetonitrile R, 30 volumes Loss on drying (2.2.32) : maximum 0.5 per cent, determined
of methanol R and 62 volumes of a 2.72 g/L solution of on 1.000 g by drying in an oven at 105 °C for 2 h.
potassium dihydrogen phosphate R previously adjusted to Sulfated ash (2.4.14): maximum 0.1 per cent, determined on
pH 7.2 with dilute sodium hydroxide solution R. 1.0 g.

4222 See the information section on general monographs (cover pages)