Dosulepin Capsules

General Notices

Action and use

Monoamine reuptake inhibitor; tricyclic antidepressant.

Definition

Dosulepin Capsules contain Dosulepin Hydrochloride.

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

Content of dosulepin hydrochloride, C19H21NS,HCl

92.5 to 107.5% of the stated amount.

Identification

Extract a quantity of the contents of the capsules containing 0.1 g of Dosulepin Hydrochloride with 20 ml of absolute ethanol, filter and remove the ethanol from the filtrate by evaporation. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of dosulepin hydrochloride (RS 114).

Tests

Related substances

Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.

(1) Extract a quantity of the contents of the capsules containing 0.25 g of Dosulepin Hydrochloride by shaking for 2 minutes with 5 ml of chloroform, centrifuge and use the supernatant liquid.
(2) Dilute 2 ml of solution (1) to 5 ml with chloroform.
(3) 0.010% w/v each of 3-(dibenzo[b,e]thiepin-11(6H)-ylidene)-N,N-dimethylaminopropan-1-amine S-oxide hydrochloride BPCRS and dibenzo[b,e]thiepin-11(6H)-one BPCRS in chloroform.
chromatographic conditions
(a) Use a TLC silica gel 60 F254 precoated plate (Merck silica gel 60 F254 plates are suitable).
(b) Use the mobile phase as described below.
(c) Apply 5 µl of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry in air and examine under ultraviolet light (254 nm).
mobile phase

1 volume of 13.5m ammonia, 10 volumes of propan-2-ol and 90 volumes of 1,2-dichloroethane.

limits

The spot with the lower Rf value in the chromatogram obtained with solution (3) is more intense than any corresponding spot in the chromatogram obtained with solution (2) (0.5%).

In the chromatogram obtained with solution (1), any secondary spot other than any spot corresponding to the spot with the lower Rf value in the chromatogram obtained with solution (3) is not more intense than the proximate spot in the chromatogram obtained with solution (3) (0.2%).

Z-Isomer

Carry out the method for gas chromatography, Appendix III B.

(1) Extract a quantity of the mixed contents of 20 capsules containing 25 mg of Dosulepin Hydrochloride with 5 ml of methanol, centrifuge and use the supernatant liquid.
(2) 0.50% w/v of dosulepin hydrochloride BPCRS in methanol.
chromatographic conditions
(a) Use a glass column (1.8 m × 3 mm) packed with acid-washed, silanised diatomaceous support (100 to 120 mesh) coated with 3% w/w of cyanopropylmethyl phenyl methyl silicone fluid (OV-225 is suitable).
(b) Use helium as the carrier gas at 1.7 ml per minute.
(c) Use isothermal conditions maintained at 200°.
(d) Use an inlet temperature of 200°.
(e) Use a flame ionisation detector at a temperature of 200°.
(f) Inject 1 µl of each solution.
limits

In the chromatogram obtained with solution (2), a peak due to Z-dosulepin is present with a retention time of approximately 0.83 relative to the retention time of the principal peak which is due to E-dosulepin.

In the chromatogram obtained with solution (1), the area of any peak corresponding to Z-dosulepin is not greater than 7.5% of the sum of the areas of the peaks due to Z-dosulepin and E-dosulepin.

Assay

Extract a quantity of the mixed contents of 20 capsules containing 0.5 g of Dosulepin Hydrochloride with 20 ml followed by four 10 ml quantities of chloroform, filtering each extract through the same filter. Evaporate the combined extracts to dryness, dissolve the residue in 100 ml of acetone, add 10 ml of mercury(ii) acetate solution and carry out Method I for non-aqueous titration, Appendix VIII A, using 3 ml of a saturated solution of methyl orange in acetone as indicator. Each ml of 0.1m perchloric acid VS is equivalent to 33.19 mg of C19H21NS,HCl.