Dosulepin Tablets
Action and use
Monoamine reuptake inhibitor; tricyclic antidepressant.
Definition
Dosulepin Tablets contain Dosulepin Hydrochloride. They are coated.
Content of dosulepin hydrochloride, C19H21NS, HCl
95.0 to 105.0% of the stated amount.
Identification
Remove the coating. Shake a quantity of the powdered tablet cores containing 0.2 g of Dosulepin Hydrochloride with 20 mL of dichloromethane, centrifuge, filter the supernatant liquid and evaporate the filtrate to dryness. Dissolve the residue in the minimum quantity of ethanol (70%) and add an excess of ether. Filter the precipitate, wash with ether and dry at 60° at a pressure of 2 kPa for 5 minutes. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of dosulepin hydrochloride (RS 114). Examine the substance as a dispersion in liquid paraffin.
Tests
Related substances
Carry out the method for thin-layer chromatography, Appendix III A, using a silica gel 60 F254 precoated plate (Merck silica gel 60 F254 plates are suitable) and a mixture of 1 volume of 13.5m ammonia, 10 volumes of propan-2-ol and 90 volumes of 1,2-dichloroethane as the mobile phase. Apply separately to the plate 5 µL of each of the following solutions. For solution (1) shake a quantity of the powdered tablets containing 0.25 g of Dosulepin Hydrochloride for 2 minutes with 5 mL of dichloromethane, centrifuge and use the supernatant liquid. For solution (2) dilute 2 mL of solution (1) to 5 mL with dichloromethane. Solution (3) contains 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. After removal of the plate, allow it to dry in air and examine under ultraviolet light (254 nm). In the chromatogram obtained with solution (3) the spot with the lower Rf value 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, using the following solutions. Solution (1) contains 0.50% w/v of dosulepin hydrochloride BPCRS in methanol. For solution (2) shake a quantity of the powdered tablets containing 25 mg of Dosulepin Hydrochloride with 5 mL of methanol for 15 minutes, centrifuge and use the supernatant liquid.
The chromatographic procedure may be carried out using 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) and maintained at 200°.
In the chromatogram obtained with solution (1) 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 (2) 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
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) shake a quantity of the powdered tablets containing 50 mg of Dosulepin Hydrochloride with 60 mL of 0.1m hydrochloric acid for 30 minutes, dilute to 100 mL with 0.1m hydrochloric acid and filter. Discard the first 25 mL of the filtrate. Dilute 25 mL of the remaining filtrate to 100 mL with 0.1m hydrochloric acid. Solution (2) contains 0.0125% w/v of dosulepin hydrochloride BPCRS in 0.1m hydrochloric acid.
The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Spherisorb ODS 1 is suitable), (b) as the mobile phase with a flow rate of 1.5 mL per minute a mixture of 10 volumes of tetrahydrofuran, 40 volumes of acetonitrile and 50 volumes of a 0.5% w/v solution of potassium dihydrogen orthophosphate, the pH of the mixture being adjusted to 3.0 with orthophosphoric acid and (c) a detection wavelength of 231 nm.
Calculate the content of C19H21NS,HCl using the declared content of C19H21NS,HCl in dosulepin hydrochloride BPCRS.