Albendazole

EUROPEAN PHARMACOPOEIA 8.0

to 105 C for 15 min. Any spot in the chromatogram obtained

with test solution (a), apart from the principal spot, is not
more intense than the spot in the chromatogram obtained
with reference solution (b) (0.5 per cent). The test is not valid
unless the chromatogram obtained with reference solution (c)
shows two clearly separated spots.
Chlorides (2.4.4). Dilute 5 mL of solution S to 15 mL with
water R. The solution complies with the limit test for chlorides
(200 ppm).
Sulfates (2.4.13). Dilute 10 mL of solution S to 15 mL with
distilled water R. The solution complies with the limit test for
sulfates (300 ppm).
Ammonium (2.4.1). 50 mg complies with limit test B for
ammonium (200 ppm). Prepare the standard using 0.1 mL of
ammonium standard solution (100 ppm NH4) R.
Iron (2.4.9). In a separating funnel, dissolve 1.0 g in 10 mL of
dilute hydrochloric acid R. Shake with three quantities, each of
10 mL, of methyl isobutyl ketone R1, shaking for 3 min each
time. To the combined organic layers add 10 mL of water R
and shake for 3 min. The aqueous layer complies with the
limit test for iron (10 ppm).
Heavy metals (2.4.8). Dissolve 2.0 g in water R and dilute to
20 mL with the same solvent. 12 mL of the solution complies
with test A for heavy metals (10 ppm). Prepare the reference
solution using lead standard solution (1 ppm Pb) R.
Loss on drying (2.2.32). Not more than 0.5 per cent,
determined on 1.000 g by drying in an oven at 105 C.
Sulfated ash (2.4.14). Not more than 0.1 per cent, determined
on 1.0 g.
ASSAY
Dissolve 80.0 mg in 3 mL of anhydrous formic acid R.
Add 30 mL of anhydrous acetic acid R. Using 0.1 mL of
naphtholbenzein solution R as indicator, titrate with 0.1 M
perchloric acid, until the colour changes from brownish-yellow
to green.
1 mL of 0.1 M perchloric acid is equivalent to 8.91 mg of
C3H7NO2.
STORAGE
Store protected from light.
01/2008:1386
corrected 6.0

ALBENDAZOLE
Albendazolum

C12H15N3O2S
[54965-21-8]

Mr 265.3

DEFINITION
Methyl [5-(propylsulfanyl)-1H-benzimidazol-2-yl]carbamate.
Content : 98.0 per cent to 102.0 per cent (dried substance).
CHARACTERS
Appearance : white or slightly yellowish powder.
Solubility : practically insoluble in water, freely soluble in
anhydrous formic acid, very slightly soluble in methylene
chloride, practically insoluble in ethanol (96 per cent).
IDENTIFICATION
Infrared absorption spectrophotometry (2.2.24).
Preparation : discs.
Comparison : albendazole CRS.

1496

TESTS
Appearance of solution. The solution is clear (2.2.1) and not
more intensely coloured than reference solution BY6 (2.2.2,
Method II).
Dissolve 0.10 g in a mixture of 1 volume of anhydrous formic
acid R and 9 volumes of methylene chloride R and dilute to
10 mL with the same mixture of solvents.
Related substances. Liquid chromatography (2.2.29).
Test solution. Dissolve 25.0 mg of the substance to be
examined in 5 mL of methanol R containing 1 per cent V/V of
sulfuric acid R and dilute to 50.0 mL with the mobile phase.
Reference solution (a). Dissolve 10.0 mg of the substance
to be examined in 10 mL of methanol R containing 1 per
cent V/V of sulfuric acid R and dilute to 100.0 mL with the
mobile phase. Dilute 0.5 mL of this solution to 20.0 mL with
the mobile phase.
Reference solution (b). Dissolve 50.0 mg of the substance
to be examined and 50 mg of oxibendazole CRS in 5 mL of
methanol R containing 1 per cent V/V of sulfuric acid R and
dilute to 100.0 mL with the mobile phase.
Column :
size : l = 0.25 m, = 4.6 mm ;
stationary phase : spherical end-capped octadecylsilyl silica
gel for chromatography R (5 m) with a pore size of 10 nm
and a carbon loading of 19 per cent.
Mobile phase : mix 300 volumes of a 1.67 g/L solution of
ammonium dihydrogen phosphate R and 700 volumes of
methanol R.
Flow rate : 0.7 mL/min.
Detection : spectrophotometer at 254 nm.
Injection : 20 L.
Run time : 1.5 times the retention time of albendazole.
Relative retention with reference to albendazole :
impurity D = about 0.40 ; impurities B and C = about 0.43 ;
impurity E = about 0.47 ; impurity F = about 0.57 ;
impurity A = about 0.80.
System suitability : reference solution (b) :
resolution : minimum 3.0 between the peaks due to
albendazole and oxibendazole.
Limits :
impurities A, B, C, D, E, F : for each impurity, not more
than 1.5 times the area of the principal peak in the
chromatogram obtained with reference solution (a)
(0.75 per cent);
total : not more than 3 times the area of the principal peak
in the chromatogram obtained with reference solution (a)
(1.5 per cent) ;
disregard limit : 0.1 times the area of the principal peak in
the chromatogram obtained with reference solution (a)
(0.05 per cent).
Loss on drying (2.2.32) : maximum 0.5 per cent, determined
on 1.000 g by drying in an oven at 105 C for 4 h.
Sulfated ash (2.4.14): maximum 0.2 per cent, determined on
1.0 g.
ASSAY
In order to avoid overheating during the titration, mix
thoroughly throughout and stop the titration immediately after
the end-point has been reached.
Dissolve 0.250 g in 3 mL of anhydrous formic acid R and add
40 mL of anhydrous acetic acid R. Titrate with 0.1 M perchloric
acid, determining the end-point potentiometrically (2.2.20).
1 mL of 0.1 M perchloric acid is equivalent to 26.53 mg
of C12H15N3O2S.
STORAGE
Protected from light.
See the information section on general monographs (cover pages)

Alcuronium chloride

EUROPEAN PHARMACOPOEIA 8.0

Reference solution. Dissolve 10 mg of alcuronium

chloride CRS in methanol R and dilute to 10 mL with the
same solvent.
Plate : TLC silica gel plate R.
Mobile phase : mix 15 volumes of a 58.4 g/L solution of
sodium chloride R, 35 volumes of dilute ammonia R2 and
50 volumes of methanol R.
A. R = S-CH2-CH2-CH3 : 5-(propylsulfanyl)-1H-benzimidazol2-amine,
Application : 10 L.
Development : over a path of 15 cm.
D. R = SO2-CH2-CH2-CH3 : 5-(propylsulfonyl)-1Hbenzimidazol-2-amine,
Drying : in air for 10 min.
Detection : spray with 0.1 M ammonium and cerium nitrate.
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.
B. R = SO-CH2-CH2-CH3 : methyl [5-(propylsulnyl)-1HC.
It gives reaction (a) of chlorides (2.3.1).
benzimidazol-2-yl]carbamate,
IMPURITIES
Specified impurities : A, B, C, D, E, F.

C. R = SO2-CH2-CH2-CH3 : methyl [5-(propylsulfonyl)-1Hbenzimidazol-2-yl]carbamate,

E. R = H : methyl (1H-benzimidazol-2-yl)carbamate,
F. R = S-CH3 : methyl [5-(methylsulfanyl)-1H-benzimidazol2-yl]carbamate.
01/2008:1285

ALCURONIUM CHLORIDE
Alcuronii chloridum

C44H50Cl2N4O2
[15180-03-7]

Mr 738

DEFINITION
(1R,3aS,10S,11aS,12R,14aS,19aS,20bS,21S,22aS,23E,26E)23,26-bis(2-Hydroxyethylidene)-1,12-bis(prop-2-enyl)2,3,11,11a,13,14,22,22a-octahydro-10H,21H-1,21:10,12diethano-19aH,20bH-[1,5]diazocino[1,2,3-lm:5,6,7lm]dipyrrolo[2,3-d:2,3 :d]dicarbazolediium dichloride
(4,4-didesmethyl-4,4-bis(prop-2-enyl)toxiferin I dichloride).
Content : 98.0 per cent to 102.0 per cent (anhydrous substance).
CHARACTERS
Appearance : white or slightly greyish-white, crystalline
powder.
Solubility : freely soluble in water and in methanol, soluble in
ethanol (96 per cent), practically insoluble in cyclohexane.
Carry out the identification, tests and assay as rapidly as
possible avoiding exposure to actinic light.
IDENTIFICATION
First identification : A, C.
Second identification : B, C.
A. Infrared absorption spectrophotometry (2.2.24).
Comparison : alcuronium chloride CRS.
B. Thin-layer chromatography (2.2.27).
Test solution. Dissolve 10 mg of the substance to be
examined in methanol R and dilute to 10 mL with the same
solvent.
General Notices (1) apply to all monographs and other texts

TESTS
Solution S. Dissolve 0.250 g in carbon dioxide-free water R
and dilute to 25.0 mL with the same solvent.
Appearance of solution. Solution S is clear (2.2.1) and not
more intensely coloured than reference solution Y6, BY6 or B6
(2.2.2, Method I).
Acidity or alkalinity. To 10 mL of solution S add 0.1 mL of
methyl red solution R and 0.2 mL of 0.01 M hydrochloric acid.
The solution is red. Add 0.4 mL of 0.01 M sodium hydroxide.
The solution is yellow.
Specic optical rotation (2.2.7) : 430 to 451 (anhydrous
substance), determined on solution S.
Propan-2-ol (2.4.24, System A): maximum 1.0 per cent.
Related substances. Liquid chromatography (2.2.29).
Solvent mixture. Mix 100 mL of methanol R, 200 mL
of acetonitrile R and 200 mL of a 6.82 g/L solution of
potassium dihydrogen phosphate R. Dissolve 1.09 g of sodium
laurylsulfonate for chromatography R in the mixture and adjust
the apparent pH to 8.0 with a 100 g/L solution of sodium
hydroxide R.
Test solution. Dissolve 0.20 g of the substance to be examined
in the solvent mixture and dilute to 100.0 mL with the solvent
mixture.
Reference solution (a). Dilute 0.5 mL of the test solution to
100.0 mL with the solvent mixture.
Reference solution (b). Dilute 4.0 mL of reference solution (a)
to 10.0 mL with the solvent mixture.
Reference solution (c). Dilute 1.0 mL of reference solution (a)
to 10.0 mL with the solvent mixture.
Reference solution (d). To 5.0 mL of the test solution add
5.0 mg of allylstrychnine bromide CRS, dissolve in the solvent
mixture and dilute to 100.0 mL with the solvent mixture.
Column :
size : l = 0.25 m, = 4 mm ;
stationary phase : octylsilyl silica gel for chromatography R
(5 m).
Mobile phase : mix 200 mL of methanol R, 400 mL of
acetonitrile R and 400 mL of a 6.82 g/L solution of
potassium dihydrogen phosphate R. Dissolve 2.18 g of sodium
laurylsulfonate for chromatography R in the mixture and adjust
the apparent pH to 5.4 with a 100 g/L solution of phosphoric
acid R.
Flow rate : 1.2 mL/min.
Detection : spectrophotometer at 254 nm.
Injection : 10 L.
Run time : twice the retention time of alcuronium.
System suitability : reference solution (d) :
resolution : minimum 4.0 between the peaks due to
N-allylstrychnine and alcuronium.

1497