Imipramine Pamoate

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

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

DOWNLOAD PDF HERE

1 DEFINITION

Imipramine Pamoate contains NLT 98.0% and NMT 102.0% of imipramine pamoate [(C₁₉H₂₄N₂) · C₂₃H₁₆O₆], calculated on anhydrous basis.

2 IDENTIFICATION

Change to read:

A. ▲Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K▲ (CN 1-May-2020)

B. The retention times of the major peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Buffer:

5.2 g/L of dibasic potassium phosphate in water

Solution A:

Acetonitrile and Buffer (15:85). Adjust with phosphoric acid to a pH of 8.0.

Solution B:

Acetonitrile and Buffer (38:62). Adjust with phosphoric acid to a pH of 8.0.

Mobile phase: See Table 1.

Diluent:

Acetonitrile and water (75:25)

Standard stock solution:

2 mg/mL of USP Imipramine Pamoate RS in Diluent

Standard solution:

0.2 mg/mL of USP Imipramine Pamoate RS from Standard stock solution in Solution A

Sample stock solution:

2 mg/mL of Imipramine Pamoate in Diluent

Sample solution:

0.2 mg/mL of Imipramine Pamoate from Sample stock solution in Solution A

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 269 nm

Column: 4.6-mm × 15-cm; 5-µm packing L1

Autosampler temperature: 10°

Flow rate: 1.5 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

[Note—Approximate relative retention times for pamoic acid and imipramine are 0.3 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between pamoic acid and imipramine

Tailing factor: NMT 1.8 for imipramine

Relative standard deviation: NMT 2.0% for imipramine

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of imipramine pamoate [(C₁₉H₂₄N₂) · C₂₃H₁₆O₆] in the portion of Imipramine Pamoate taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of imipramine from the Sample solution

rₛ = peak response of imipramine from the Standard solution

Cₛ = concentration of USP Imipramine Pamoate RS in the Standard solution (mg/mL)

Cᵤ = concentration of Imipramine Pamoate in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the anhydrous basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.10%

Organic Impurities

Buffer:

5.2 g/L of dibasic potassium phosphate in water

Solution A:

Acetonitrile and Buffer (38:62). Adjust with phosphoric acid to a pH of 7.9.

Solution B:

Acetonitrile and Buffer (70:30). Adjust with phosphoric acid to a pH of 6.0.

Mobile phase: See Table 2.

Diluent:

Acetonitrile and water (75:25)

System suitability solution:

0.5 mg/mL of USP Imipramine Pamoate RS,

0.02 mg/mL of USP Depramine RS, and

0.02 mg/mL USP Iminodibenzyl RS in Diluent

Standard solution:

0.002 mg/mL of USP Imipramine Pamoate RS in Diluent

Sample solution:

2 mg/mL of Imipramine Pamoate in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 15-cm; 5-µm packing L1

Temperatures

Column: 40°

Autosampler: 10°

Flow rate: 1.0 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

[Note—See Table 3 for relative retention times.]

Suitability requirements

Resolution: NLT 5.0 between imipramine and depramine, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Imipramine Pamoate taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of each impurity from the Sample solution

rₛ = peak response of imipramine from the Standard solution

Cₛ = concentration of USP Imipramine Pamoate RS in the Standard solution (mg/mL)

Cᵤ = concentration of Imipramine Pamoate in the Sample solution (mg/mL)

Acceptance criteria: See Table 3. Disregard peaks that are less than 0.05% of the imipramine peak.

ᵃ Pamoic acid is not an impurity. It is listed for identification purposes only.

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

5 SPECIFIC TESTS

Water Determination, Method I 〈921〉: NMT 2.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP Depramine RS

3-(5H-Dibenzo[b,f]azepin-5-yl)-N,N-dimethylpropan-1-amine.

C₁₉H₂₂N₂ 278.39

USP Iminodibenzyl RS

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

C₁₄H₁₃N 195.28

USP Imipramine Pamoate RS