Amitriptyline Tablets

General Notices

Action and use

Monoamine reuptake inhibitor; tricyclic antidepressant.

Definition

Amitriptyline Tablets contain Amitriptyline Hydrochloride. They are coated.

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

Content of amitriptyline hydrochloride, C20H23N,HCl

90.0 to 110.0% of the stated amount.

Identification

A. Shake a quantity of the powdered tablets containing 5 mg of Amitriptyline Hydrochloride 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 powdered tablets containing 0.1 g of Amitriptyline Hydrochloride 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 water and add 0.05 mL of a 2.5% w/v solution of quinhydrone in methanol. No red colour is produced within 15 minutes (distinction from nortriptyline).
C. The precipitate obtained in test B yields reaction A characteristic of chlorides, Appendix VI.

Tests

Related substances

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

(1) Extract a quantity of the powdered tablets containing 20 mg of Amitriptyline Hydrochloride 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 BPCRS in chloroform.
(3) 0.0040% w/v of cyclobenzaprine hydrochloride BPCRS.
chromatographic conditions
(a) Use as the coating silica gel G.
(b) Use the mobile phase as described below.
(c) Apply 10 µL of each solution.
(d) Develop the plate to 14 cm.
(e) After removal of the plate, dry in air, spray with a freshly prepared mixture of 4 volumes of formaldehyde and 96 volumes of sulfuric acid, heat at 100° to 105° for 10 minutes.
mobile phase

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

limits

Examine the plate 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) (0.25%).

Examine the plate under ultraviolet light (254 nm):

any other secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (3) (1%).

Assay

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) For film-coated tablets Add 50 mL of 0.1m hydrochloric acid to 20 tablets, shake vigorously until the tablets are completely disintegrated, add 100 mL of methanol and shake for 30 minutes. Dilute the suspension to 200 mL with methanol, centrifuge and dilute a volume of the supernatant liquid containing 25 mg of Amitriptyline Hydrochloride to 100 mL with methanol (50%). For sugar-coated tablets Shake a quantity of the powder containing 50 mg of Amitriptyline Hydrochloride with 50 mL of 0.1m hydrochloric acid for 30 minutes, add 100 mL of methanol and shake for 30 minutes. Dilute the suspension to 200 mL with water, centrifuge and use the supernatant liquid.
(2) Dissolve 50 mg of amitriptyline hydrochloride BPCRS in 10 mL of methanol and dilute to 200 mL with 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

0.03m sodium hexanesulfonate in a mixture of equal volumes of water and acetonitrile, adjusted to pH 4.5 by the addition of glacial acetic acid,

determination of content

Calculate the content of C20H23N,HCl using the declared content of C20H23N,HCl in amitriptyline hydrochloride BPCRS.