Co-danthrusate Capsules

General Notices

Dantron and Docusate Sodium Capsules

Action and use

Stimulant laxative.

Definition

Co-danthrusate Capsules contain Dantron and Docusate Sodium in the proportions, by weight, 5 parts to 6 parts.

The capsules comply with the requirements stated under Capsules and with the following requirements.

Content of dantron, C14H8O4

90.0 to 110.0% of the stated amount.

Content of docusate sodium, C20H37NaO7S

90.0 to 110.0% of the stated amount.

Identification

A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Shake a quantity of the contents of the capsules containing 50 mg of Dantron with 10 mL of dichloromethane, filter and dilute 2 mL of the filtrate to 20 mL with dichloromethane.
(2) 0.06% w/v of docusate sodium BPCRS in dichloromethane.
(3) 0.05% w/v of dantron BPCRS in dichloromethane.
chromatographic conditions
(a) Use as the coating silica gel F254 (Merck silica gel 60 F254 plates are suitable).
(b) Use the mobile phase described below.
(c) Apply 10 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, allow it to dry in air, spray with ethanolic sulfuric acid (10%) and heat at 120° for 15 minutes. Examine in daylight.
mobile phase

15 volumes of methanol and 85 volumes of ethyl acetate.

confirmation

The two principal spots in the chromatogram obtained with solution (1) correspond to the principal spots in the chromatograms obtained with solutions (2) and (3).

B. Shake a quantity of the contents of the capsules containing 60 mg of Docusate Sodium with 50 mL of water. To 5 mL of this mixture add 1 mL of 2m sulfuric acid, 10 mL of dichloromethane and 0.2 mL of dimethyl yellow solution and mix; a red colour is produced in the dichloromethane layer. Add 50 mg of cetrimide and mix; the dichloromethane layer is yellow.
C. To a quantity of the contents of the capsules containing 50 mg of Dantron add 10 mL of dichloromethane and 5 mL of 1m ammonia and mix. A red colour is produced in the aqueous layer.

TEST

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Shake a quantity of the mixed contents of 20 capsules containing 50 mg of Dantron with 20 mL of tetrahydrofuran for 5 minutes and dilute to 100 mL with the mobile phase.
(2) Dilute 1 volume of solution (1) to 50 volumes with the mobile phase.
(3) Dissolve 50 mg of dantron impurity standard BPCRS in 20 mL of tetrahydrofuran and dilute to 100 mL with the mobile phase.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Nucleosil C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 254 nm.
(f) Inject 20 µL of each solution.
(g) For solution (2), allow the chromatography to proceed for 1.5 times the retention time of the principal peak.
mobile phase

2.5 volumes of glacial acetic acid, 40 volumes of tetrahydrofuran and 60 volumes of water.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (3):

a peak due to 1-hydroxyanthraquinone appears immediately before the principal peak, as indicated in the reference chromatogram supplied with dantron impurity standard BPCRS;

the height of the trough separating the two peaks is not greater than one third of the height of the peak due to 1-hydroxyanthraquinone.

limits

In the chromatogram obtained with solution (1):

the area of any peak corresponding to 1-hydroxyanthraquinone is not greater than 2.5 times the area of the principal peak in the chromatogram obtained with solution (2) (3.3% taking into account the correction factor for the impurity);

the sum of the areas of any other secondary peaks is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (2%).

Disregard any peak with a retention time less than one third of that of the principal peak.

Assay

For dantron

To a quantity of the mixed contents of 20 capsules containing 35 mg of Dantron add 50 mL of absolute ethanol, heat on a water bath for 30 minutes and cool. Add sufficient absolute ethanol to produce 100 mL and filter through glass-fibre paper (Whatman GF/C is suitable). Dilute 5 mL of the filtrate to 100 mL with absolute ethanol and measure the absorbance of the resulting solution at the maximum at 430 nm, Appendix II B. Calculate the content of C14H8O4 taking 458 as the value of A(1%, 1 cm) at the maximum at 430 nm.

For docusate sodium

To a quantity of the mixed contents of 20 capsules containing 0.3 g of Docusate Sodium add 25 mL of absolute ethanol, heat to 60° for 5 minutes and cool. Add sufficient water to produce 200 mL and filter through glass-fibre paper (Whatman GF/C is suitable). To 25 mL of the filtrate add 10 mL of water and 15 mL of chloroform and titrate with 0.004m benzethonium chloride VS, using dimidium bromide-sulfan blue mixed solution as indicator, to the first appearance of a green colour in the chloroform layer and shaking vigorously towards the end point. Each mL of 0.004m benzethonium chloride VS is equivalent to 1.778 mg of C20H37NaO7S.