Nortriptyline Capsules

General Notices

Action and use

Monoamine reuptake inhibitor; tricyclic antidepressant.

Definition

Nortriptyline Capsules contain Nortriptyline Hydrochloride.

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

Content of nortriptyline, C₁₉H₂₁N

92.5 to 107.5% of the stated amount.

Identification

A. Shake a quantity of the contents of the capsules 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 solution, Appendix II B, in the range 230 to 350 nm exhibits a maximum only at 265 nm.

B. Triturate a quantity of the contents of the capsules containing the equivalent of 0.1 g of nortriptyline with 10 mL of chloroform, filter and evaporate the chloroform. Dissolve 50 mg of the residue 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 residue 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 silica gel G as the coating substance and a mixture of 3 volumes of diethylamine, 15 volumes of ethyl acetate and 85 volumes of cyclohexane as the mobile phase but allowing the solvent front to ascend 12 cm above the line of application. Apply separately to the plate 5 µL of each of the following solutions. For solution (1) extract a quantity of the contents of the capsules 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. Solution (2) contains 0.0010% w/v of dibenzosuberone in ethanol (96%). After removal of the plate, allow it to 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). 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) (0.5%).

Assay

Carry out Method I for non-aqueous titration, Appendix VIII A, using a quantity of the mixed contents of 20 capsules containing the equivalent of 0.1 g of nortriptyline, adding 3 mL of mercury(ii) acetate solution and using 0.02m perchloric acid VS as titrant and crystal violet solution as indicator. Each mL of 0.02m perchloric acid VS is equivalent to 5.268 mg of C₁₉H₂₁N.

Labelling

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