Imipramine Hydrochloride Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Imipramine Hydrochloride Tablets contain NLT 93.0% and NMT 107.0% of the labeled amount of imipramine hydrochloride (C₁₉H₂₄N₂ . HCI).

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K

Sample: Powder a suitable number of Tablets, equivalent to 100 mg of imipramine hydrochloride, and macerate the powder with 10 mL of chloroform. Filter the chloroform extract through paper into a wide-mouth test tube, and evaporate the filtrate to 3 mL. Carefully add ether until the liquid becomes turbid, heat on a steam bath to produce a clear solution, cool, and allow to stand. The precipitate that is formed may be recrystallized from acetone. Filter the crystalline precipitate, wash with ether, and dry under vacuum at 105° for 30 min. Use the precipitate.

Acceptance criteria: Meet the requirements

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 PROCEDURE

Solution A: 0.02 M ammonium bicarbonate in water. Adjust with 28%-30% ammonia solution to a pH of 8.0.

Solution B: Acetonitrile and methanol (70:30)

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (40:60)

Standard solution: 0.25 mg/mL of USP Imipramine Hydrochloride RS in Diluent

Sample stock solution: Nominally 1.0 mg/mL of imipramine hydrochloride from Tablets prepared as follows. Powder NLT 10 Tablets and transfer a sufficient portion of powder to a volumetric flask. Add 75% of the final flask volume of Diluent. Sonicate as needed to aid in dissolution. Allow to cool to room temperature, then dilute with Diluent to volume. Centrifuge and use the supernatant. [NOTE-The use of a centrifuge speed of 3000 rpm for 10 min may be suitable.]

Sample solution: Nominally 0.25 mg/mL of imipramine hydrochloride from Sample stock solution in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 2.1-mm x 10-cm, 1.7-µm packing L7

Column temperature: 35°

Flow rate: 0.4 mL/min

Injection volume: 2 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of imipramine hydrochloride (C₁₉H₂₄N₂ . HCI) in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution s

C_S = concentration of USP Imipramine Hydrochloride RS in the Standard solution (mg/mL)

C_U = nominal concentration of imipramine hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 93.0%-107.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

Medium: 0.01 N hydrochloric acid; 900 mL

Apparatus 1: 100 rpm

Time: 45 min

Mode: UV-Vis

Analytical wavelength: UV 250 nm

Standard solution: USP Imipramine Hydrochloride RS in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter. Dilute with Medium to a suitable concentration.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of imipramine hydrochloride (C₁₉H₂₄N₂ . HCI) dissolved:

Result = (A_U/A_S) x C_S x D x V x (1/L) x 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of USP Imipramine Hydrochloride RS in the Standard solution (mg/mL)

D = dilution factor for the Sample solution, if needed

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of imipramine hydrochloride (C₁₉H₂₄N₂ . HCI) is dissolved.

Change to read:

4.2 UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements (CN 1-Aug-2023)

Procedure for content uniformity

Diluent: Hydrochloric acid and water (1:100)

Standard solution: 0.025 mg/mL of USP Imipramine Hydrochloride RS in Diluent

Sample stock solution: Transfer 1 finely powdered Tablet to a 100-mL volumetric flask with the aid of 70 mL of Diluent and shake by mechanical means for 30 min. Dilute with Diluent to volume, and filter, if necessary, discarding the first 20 mL of the filtrate.

Sample solution: Nominally 0.025 mg/mL of imipramine hydrochloride from Sample stock solution in Diluent

Instrumental conditions

Mode: UV-Vis

Analytical wavelength: UV 250 nm

Cell: 1 cm

Blank: Diluent

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of imipramine hydrochloride (C₁₉H₂₄N₂ . HCI) in the Tablet taken:

Result = (A_U/A_S) × (C_S/C_U) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of USP Imipramine Hydrochloride RS in the Standard solution (mg/mL)

C_U = nominal concentration of imipramine hydrochloride in the Sample solution (mg/mL)

(CN 1-Aug-2023)

5 IMPURITIES

5.1 ORGANIC IMPURITIES

Solution A, Solution B, Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 0.002 mg/mL each of USP Imipramine Hydrochloride RS, USP Depramine RS, USP Desipramine Hydrochloride RS, and USP Iminodibenzyl RS in Diluent. Sonicate if necessary to aid dissolution.

Sample solution: Nominally 1.0 mg/mL of imipramine hydrochloride from Tablets prepared as follows. Powder NLT 10 Tablets and transfer a portion to a volumetric flask. Add about 75% of the final flask volume of Diluent. Sonicate as necessary to aid dissolution. Allow to cool to room temperature, then dilute with Diluent to volume. Centrifuge and use the supernatant. [NOTE-The use of a centrifuge speed of 3000 rpm for 10 min may be suitable.]

System suitability

Sample: Standard solution

[NOTE-The relative retention times for desipramine, depramine, imipramine, and iminodibenzyl are 0.82, 0.84, 1.0, and 1.18, respectively.]

Suitability requirements

Resolution: NLT 1.5 between the depramine and desipramine peaks

Relative standard deviation: NMT 2.5% each for desipramine, imipramine, and iminodibenzyl

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of desipramine and iminodibenzyl in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of desipramine or iminodibenzyl from the Sample solution

r_S = peak response of USP Desipramine Hydrochloride RS or USP Iminodibenzyl RS from the Standard solution

C_S = concentration of USP Desipramine Hydrochloride RS or USP Iminodibenzyl RS in the Standard solution (mg/mL)

C_U = nominal concentration of imipramine hydrochloride in the Sample solution (mg/mL)

Calculate the percentage of each unspecified degradation product in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each unspecified degradation product from the Sample solution

r_S = peak response of imipramine from the Standard solution

C_S = concentration of USP Imipramine Hydrochloride RS in the Standard solution (mg/mL)

C_U = nominal concentration of imipramine hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. Disregard any impurity peaks less than 0.05%.

Table 2

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers. Store at controlled room temperature.

USP REFERENCE STANDARDS (11)

USP Depramine RS

3-(5H-Dibenzo[b, fazepin-5-yl)-N,N-dimethylpropan-1-amine hydrochloride.

C₁₉H₂₂N₂ . HCI  314.85

USP Desipramine Hydrochloride RS

10,11-Dihydro-5H-[3-(methylamino)propyl]-5H-dibenz[b,flazepine monohydrochloride.

C₁₈H₂₂N₂ . HCI  302.84

USP Iminodibenzyl RS

10,11-Dihydro-5H-dibenzo[b,f]azepine.

C₁₄H₁₃N  195.28

USP Imipramine Hydrochloride RS