Tetryzoline Hydrochloride

(Ph Eur monograph 2101)

C₁₃H₁₇ClN₂    236.7    522-48-5

Adrenoceptor agonist; decongestant.

Ph Eur

2-[(1RS)-1,2,3,4-Tetrahydronaphthalen-1-yl]-4,5-dihydro-1H-imidazole hydrochloride.

98.0 per cent to 101.0 per cent (dried substance).

White or almost white, crystalline powder.

Freely soluble in water, in anhydrous ethanol and in ethanol (96 per cent), practically insoluble in acetone.

A.  Infrared absorption spectrophotometry (2.2.24).

Comparison  tetryzoline hydrochloride CRS.

B.  Dissolve 50 mg in 10 ml of water R. The solution gives reaction (a) of chlorides (2.3.1).

The solution is clear (2.2.1) and colourless (2.2.2, Method II).

Dissolve 1.0 g in water R and dilute to 10 ml with the same solvent.

Gas chromatography (2.2.28).

Test solution  Dissolve 1.0 g of the substance to be examined in a mixture of 25 volumes of 1 M sodium hydroxide and 75 volumes of methanol R and dilute to 10 ml with the same mixture of solvents.

Reference solution  Dilute 1.0 ml of the test solution to 100.0 ml with a mixture of 25 volumes of 1 M sodium hydroxide and 75 volumes of methanol R. Dilute 1.0 ml of this solution to 10.0 ml with a mixture of 25 volumes of 1 M sodium hydroxide and 75 volumes of methanol R.

• — material: fused silica;

• — size: l  =  25 m, Ø = 0.32 mm;

• — stationary phase: poly(dimethyl)siloxane R (1 µm).

Carrier gas  helium for chromatography R.

Split ratio  1:40.

Flow rate  2.5 ml/min.

Temperature:

Detection  Flame ionisation.

Injection  1 µl.

Relative retention  With reference to tetryzoline (retention time  =  about 12 min): impurity A  =  about 0.5.

System suitability  Reference solution:

• — signal-to-noise ratio: minimum 50 for the principal peak.

• — impurity A: not more than the area of the principal peak in the chromatogram obtained with the reference solution (0.1 per cent);

• — any other impurity: for each impurity, not more than the area of the principal peak in the chromatogram obtained with the reference solution (0.1 per cent);

• — total: not more than twice the area of the principal peak in the chromatogram obtained with the reference solution (0.2 per cent);

• — disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with the reference solution (0.05 per cent).

Maximum 0.5 per cent, determined on 1.000 g by drying in an oven at 105 °C.

Maximum 0.1 per cent, determined on 1.0 g.

Dissolve 0.200 g in 100 ml of a mixture of 3 volumes of anhydrous acetic acid R and 7 volumes of acetic anhydride R. Titrate with 0.1 M perchloric acid, determining the end-point potentiometrically (2.2.20). Carry out a blank titration.

1 ml of 0.1 M perchloric acid is equivalent to 23.67 mg of C₁₃H₁₇ClN₂.

Specified impurities  A.

A.  (1RS)-1,2,3,4-tetrahydronaphthalene-1-carbonitrile (α-cyanotetraline).

Ph Eur