Mianserin Hydrochloride

(Ph Eur monograph 0846)

 

C18H20N2,HCl 300.8 21535-47-7

 

Ph Eur


 

 

Definition

 

Mianserin hydrochloride contains not less than 98.5 per cent and not more than the equivalent of 101.0 per cent of (RS)-2-methyl-1,2,3,4,10,14b- hexahydrodibenzo[c,f]pyrazino[1,2-a]azepine hydrochloride, calculated with reference to the dried substance.

 

Characters

 

White or almost white, crystalline powder or crystals, sparingly soluble in water, soluble in methylene chloride, slightly soluble in alcohol.

 

Identification

 

First identification

 

B, D.

 

Second identification

 

A, C, D.

 

A.    Dissolve 50.0 mg in water  R and dilute to 50.0 ml with the same solvent. Dilute 5.0 ml of the solution to 50.0 ml with water  R. Examined between 230 nm and 350 nm (2.2.25), the solution shows an absorption maximum at 279 nm. The specific absorption at the maximum is 64 to 72.

 

B.    Examine by infrared absorption spectrophotometry (2.2.24), comparing with the spectrum obtained with mianserin hydrochloride CRS. Examine the substances as discs prepared using potassium chloride R. If the spectra obtained show differences, dissolve the substance to be examined and the reference substance separately in methanol  R, evaporate to dryness and record new spectra using the residues.

 

C.    Examine by thin-layer chromatography (2.2.27), using silica gel GF254 R as the coating substance.

 

Test solution

 

Dissolve 10 mg of the substance to be examined in methylene chloride R and dilute to 5 ml with the same solvent.

 

Reference solution (a)

 

Dissolve 10 mg of mianserin hydrochloride CRS in methylene chloride R and dilute to 5 ml with the same solvent.

 

Reference solution (b)

 

Dissolve 10 mg of mianserin hydrochloride CRS and 10 mg of cyproheptadine hydrochloride CRS in methylene chloride R and dilute to 5 ml with the same solvent.

 

Apply to the plate 2 ml of each solution. Develop over a path of 15 cm using a mixture of 5 volumes of diethylamine R, 20 volumes of ether  R and 75 volumes of cyclohexane R. Examine in ultraviolet light at 254 nm. The principal spot in the chromatogram obtained with the test solution is similar in position and size to the principal spot in the chromato-gram obtained with reference solution (a). The test is not valid unless the chromatogram obtained with reference solution (b) shows two clearly separated principal spots.

 

D. It gives reaction (a) of chlorides (2.3.1).

 

Tests

 

pH (2.2.3)

 

Dissolve 0.10 g in carbon dioxide-free water  R and dilute to 10 ml with the same solvent. The pH of the solution is 4.0 to 5.5.

 

Related substances

 

Examine by thin-layer chromato-graphy (2.2.27), using silica gel G R as the coating substance.

 

Test solution

 

Dissolve 0.20 g of the substance to be examined in a mixture of 1 volume of ammonia R and 4 volumes of methanol  R and dilute to 10 ml with the same mixture of solvents.

 

Reference solution (a)

 

Dilute 1 ml of the test solution to 200 ml with a mixture of 1 volume of ammonia R and 4 volumes of methanol  R.

 

Reference solution (b)

 

Dilute 5 ml of reference solution (a) to 25 ml with a mixture of 1 volume of ammonia R and 4 volumes of methanol  R.

 

Apply to the plate 5 ml of each solution. Develop over a path of 15 cm using a mixture of 10 volumes of methanol  R and 90 volumes of methylene chloride R. Dry the plate in a current of cold air. Expose the plate to iodine vapour for 20 min. Any spot in the chromatogram obtained with the test solution, apart from the principal spot, is not more intense than the spot in the chromatogram obtained with reference solution (a) (0.5 per cent) and at most one such spot is more intense than the spot in the chromatogram obtained with reference solution (b) (0.1 per cent).

 

Loss on drying (2.2.32)

 

Not more than 0.5 per cent, determined on 1.000 g by drying over diphosphorus pentoxide R at 65C at a pressure not exceeding 700 Pa for 3 h.

 

Sulphated ash (2.4.14)

 

Not more than 0.1 per cent, determined on 1.0 g.

 

Assay

 

Dissolve 0.200 g in a mixture of 5.0 ml of 0.01M hydrochloric acid and 50 ml of alcohol  R. Carry out a potentiometric titration (2.2.20), using 0.1M sodium hydroxide. Read the volume added between the two points of inflexion.

 

l ml of 0.1M sodium hydroxide is equivalent to 30.08 mg of C18H21ClN2.

 

Storage

 

Store protected from light.

 

Impurities

 

A.    [2-[(2RS)-4-methyl-2-phenylpiperazin-1-yl]phenyl]methanol.

 

 


 Ph Eur

 

Action and use

 

Antidepressant.

 

Preparation

 

Mianserin Tablets