Molecular formula. C₂₇H₂₂Cl₂N₄

Relative molecular mass. 473.4

Graphic formula.

Chemical name. 3-(p-Chloroanilino)-10-(p-chlorophenyl)-2,10-dihydro-2-(isopropylimino)phenazine; N,5-bis(4-chlorophenyl)-3,5-dihydro-3-[(1-methylethyl)imino]-2-phenazinamine; CAS Reg. No. 2030-63-9.

Description. A reddish brown, fine powder; odourless or almost odourless.

Solubility. Practically insoluble in water; slightly soluble in ethanol (~750 g/l) TS and in ether R.

Category. Antileprosy drug.

Storage. Clofazimine should be kept in a well-closed container.

Additional information. Clofazimine melts at about 217 °C.

Requirements

Definition. Clofazimine contains not less than 98.0% and not more than 101.0% of C₂₇H₂₂Cl₂N₄, calculated with reference to the dried substance.

Identity tests

• Either test A or tests B and C 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 clofazimine RS or with the reference spectrum of clofazimine.

B. The absorption spectrum of a 5.0 μg/mL solution in hydrochloric acid/methanol (0.01 mol/l) VS, when observed between 230 nm and 600 nm, exhibits 2 maxima at about 283 nm and 487 nm. The absorbances of a 1-cm layer at these wavelengths are about 0.65 and 0.32, respectively.

C. Dissolve about 2 mg in 3 mL of acetone R and add 0.1 mL of hydrochloric acid (~420 g/l) TS; an intense violet colour is produced. Add 0.5 mL of sodium hydroxide (~200 g/l) TS; the colour changes to orange-red.

Heavy metals. Use 1.0 g for the preparation of the test solution as described under 2.2.3 Limit test for heavy metals, Procedure 3; determine the heavy metals content according to Method A; not more than 10 μg/g.

Sulfated ash. Not more than 1.0 mg/g.

Loss on drying. Dry to constant weight at 105°C; it loses not more than 5.0 mg/g.

Related substances. Carry out the test as described under 1.14.1 Chromatography, Thin-layer chromatography, using silica gel R6 (a precoated plate from a commercial source is suitable), exposed immediately before use to ammonia vapour by suspending the plate for 30 minutes in a chromatographic chamber containing a shallow layer of ammonia (~17 g/l) TS. As the mobile phase, to be used in a separate chamber, prepare a mixture of 85 volumes of dichloromethane R and 4 volumes of 1-propanol R. Apply separately to the plate 5 μl of each of 3 solutions in chloroform R containing (A) 20 mg of the test substance per mL, (B) 0.16 mg of the test substance per mL, and (C) 0.10 mg of the test substance per mL. Allow the mobile phase to ascend 12 cm above the line of application. After removing the plate from the chromatographic chamber, allow it to dry in air for 5 minutes, and replace it in the chamber. Allow the mobile phase to ascend again 12 cm, remove the plate from the chamber, dry it in air for 5 minutes, 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 spot obtained with solution C, except that 2 such spots are not more intense than that obtained with solution B.

Assay. Dissolve about 0.4 g, accurately weighed, in 20 mL of chloroform R, add 50 mL of acetone R, and titrate with perchloric acid (0.1 mol/l) VS as described under 2.6 Non-aqueous titration, Method A. Each mL of perchloric acid (0.1 mol/l) VS is equivalent to 47.34 mg of C₂₇H₂₂Cl₂N₄.