Monographs: Pharmaceutical substances: Albendazolum - Albendazole

C₁₂H₁₅N₃O₂S

Relative molecular mass. 265.3

Chemical name. Methyl 5-(propylthio)-2-benzimidazolecarbamate; CAS Reg. No. 54965-21-8.

Description. A white or almost white powder.

Solubility. Practically insoluble in water; soluble in glacial acetic acid R; slightly soluble in acetone R, very slightly soluble in ethanol (~750 g/l) TS.

Category. Anthelminthic.

Storage. Albendazole should be kept in a well-closed container, protected from light.

Additional information. Melting temperature, about 210°C, with decomposition.

Requirements

Albendazole contains not less than 98.0% and not more than 101.0% of C₁₂H₁₅N₃O₂S, calculated with reference to the dried substance.

Identity tests

• Either test A alone or tests B, C, and D may be applied.

A. Carry out the examination as described under 1.7 Spectrophotometry in the infrared region. The infrared absorption spectrum is concordant with the spectrum obtained from albendazole RS or with the reference spectrum of albendazole.

B. See the test described below under "Related substances". The principal spot obtained with solution B corresponds in position, appearance, and intensity with that obtained with solution C.

C. Ignite about 0.1 g; fumes are evolved, staining lead acetate paper R black.

D. Add about 0.1 g to 3 ml of sulfuric acid (~100 g/l) TS and warm to dissolve. Add about 1ml of potassium iodobismuthate/acetic acid TS; a reddish brown precipitate is produced.

Sulfated ash. Not more than 1.0 mg/g.

Loss on drying. Dry at 105 °C for 4 hours; it loses not more than 5.0 mg/g.

Related substances. Carry out the test as described under 1.14.1 Thin-layer chromatography, using silica gel R2 as the coating substance and a mixture of 6 volumes of dichloromethane R, 1 volume of ether R, and 1 volume of glacial acetic acid R as the mobile phase. Apply separately to the plate 10 μl of each of 5 solutions in a mixture of 9 volumes of dichloromethane R and 1 volume of anhydrous formic acid R containing (A) 10.0 mg of Albendazole per ml, (B) 1.0 mg of Albendazole per ml, (C) 1.0mg of albendazole RS per ml, (D) 0.05 mg of albendazole RS per ml, and (E) 0.025 mg of albendazole RS per ml. After removing the plate from the chromatographic chamber, allow it to dry in a current of warm air, and examine the chromatogram in ultraviolet light (254 nm).

Any spot obtained with solution A, other than the principal spot, is not more intense than the principal spot obtained with solution D (0.5%), and only one spot may be more intense than the principal spot obtained with solution E (0.25%).

Assay. Dissolve about 0.25 g, accurately weighed, in 3ml of anhydrous formic acid R, and add 40 ml of glacial acetic acid R1. Then add 0.2 ml of 1-naphtholbenzein/acetic acid TS and titrate with perchloric acid (0.1 mol/l) VS until a green colour is obtained as described under 2.6 Non-aqueous titration, Method A.

Each ml of perchloric acid (0.1 mol/l) VS is equivalent to 26.53mg of C₁₂H₁₅N₃O₂S.