Nortriptyline Tablets

General Notices

Action and use

Monoamine reuptake inhibitor; tricyclic antidepressant.

Definition

Nortriptyline Tablets contain Nortriptyline Hydrochloride. They are coated.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of nortriptyline, C19H21N

90.0 to 110.0% of the stated amount.

Identification

A. Shake a quantity of the powdered tablets containing the equivalent of 5 mg of nortriptyline with 20 mL of methanol and filter. To 1 mL of the filtrate add 1 mL of a 2.5% w/v solution of sodium hydrogen carbonate, 1 mL of a 2% w/v solution of sodium periodate and 1 mL of a 0.3% w/v solution of potassium permanganate. Allow to stand for 15 minutes, acidify with 1m sulfuric acid and extract with 10 mL of 2,2,4-trimethylpentane. The light absorption of the resulting trimethylpentane solution, Appendix II B, in the range 230 to 350 nm exhibits a maximum only at 265 nm.
B. Triturate a quantity of the powdered tablets containing the equivalent of 0.1 g of nortriptyline with 10 mL of chloroform, filter and evaporate the filtrate to a low volume. Add ether until a turbidity is produced and allow to stand. Dissolve 50 mg of the precipitate in 3 mL of warm water, cool and add 0.05 mL of a 2.5% w/v solution of quinhydrone in methanol. A red colour develops (distinction from amitriptyline).
C. The precipitate obtained in test B yields reaction A characteristic of chlorides, Appendix VI.

Tests

Dibenzosuberone

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

(1) Extract a quantity of the powdered tablets containing the equivalent of 20 mg of nortriptyline with 5 mL of a mixture of 1 volume of 2m hydrochloric acid and 9 volumes of ethanol (96%), centrifuge and use the supernatant liquid.
(2) 0.0010% w/v of dibenzosuberone in ethanol (96%).
chromatographic conditions
(a) Use as the coating silica gel G.
(b) Use the mobile phase as described below.
(c) Apply 5 µL of each solution.
(d) Develop the plate to 12 cm.
(e) After removal of the plate, dry in air until the solvent has evaporated, spray with sulfuric acid containing 4% v/v of formaldehyde solution and examine immediately under ultraviolet light (365 nm).
mobile phase

3 volumes of diethylamine, 15 volumes of ethyl acetate and 85 volumes of cyclohexane.

limits

Any spot corresponding to dibenzosuberone in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) (0.25%).

Assay

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

(1) Add 50 mL of water to 20 tablets, shake vigorously until the tablets have completely disintegrated, add 100 mL of methanol and shake for 30 minutes. Add sufficient water to produce 200 mL, filter and dilute a volume of the filtrate containing the equivalent of 25 mg of nortriptyline to 100 mL with methanol (50%).
(2) 0.025% w/v solution of nortriptyline hydrochloride BPCRS in methanol (50%). 
chromatographic conditions
(a) Use a stainless steel column (20 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (10 µm) (Nucleosil C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 239 nm.
(f) Inject 20 µL of each solution.
mobile phase

0.56% w/v solution of sodium hexanesulfonate in a mixture of equal volumes of water and acetonitrile adjusted to pH 4.5 with glacial acetic acid.

determination of content

Calculate the content of C19H21N using the declared content of C19H21N in nortriptyline hydrochloride BPCRS.

Labelling

The quantity of active ingredient is stated in terms of the equivalent amount of nortriptyline.