Desipramine Hydrochloride

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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C₁₈H₂₂N₂·HCl 302.84

5H-Dibenz[b,f]azepine-5-propanamine, 10,11-dihydro-N-methyl-, monohydrochloride;

10,11-Dihydro-5-[3-(methylamino)propyl]-5H-dibenz[b,f]azepine monohydrochloride   CAS RN®: 58-28-6; UNII: 1Y58DO4MY1.

1 DEFINITION

Desipramine Hydrochloride contains NLT 98.0% and NMT 102.0% of desipramine hydrochloride (C₁₈H₂₂N₂·HCl).

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M

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

C. Identification Tests-General, Chloride 〈191〉

• Sample solution: 50 mg/mL of Desipramine Hydrochloride in alcohol
• Acceptance criteria: Meets the requirements

3 ASSAY

3.1 Procedure

Buffer: 3.4 g/L of sodium acetate trihydrate in water adjusted with glacial acetic acid to a pH of 5.0

Mobile phase: Acetonitrile, methanol, and Buffer (35:20:45)

Diluent: 0.1 M hydrochloric acid

System suitability solution: 0.02 mg/mL each of USP Desipramine Hydrochloride RS and USP Imipramine Hydrochloride RS in Diluent. Sonication may be used to promote dissolution.

Standard solution: 0.1 mg/mL of USP Desipramine Hydrochloride RS in Diluent. Sonication may be used to promote dissolution.

Sample solution: 0.1 mg/mL of Desipramine Hydrochloride in Diluent. Sonication may be used to promote dissolution.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 250 nm
• Column: 4.6-mm × 25-cm; 5-µm packing L10
• Flow rate: 1 mL/min
• Injection volume: 25 µL

System suitability

• Samples: System suitability solution and Standard solution
• [Note-The relative retention times for desipramine and imipramine are 1.0 and 1.1, respectively.]
• Suitability requirements
• Resolution: NLT 1.5 between desipramine and imipramine, System suitability solution
• Tailing factor: NMT 2, Standard solution
• Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of desipramine hydrochloride (C₁₈H₂₂N₂·HCl) in the portion of Desipramine Hydrochloride 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

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

C_u = concentration of Desipramine Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0%

4 IMPURITIES

4.1 Residue on Ignition 〈281〉: NMT 0.1%

4.2 Organic Impurities

Buffer: 5.2 g/L of dibasic potassium phosphate in water. Add 1 mL of triethylamine per L, and adjust with phosphoric acid to a pH of 6.4.

Solution A: Acetonitrile and methanol (55:45)

Solution B: Solution A and Buffer (25:75)

Solution C: Solution A and Buffer (62.5:37.5)

Mobile phase: See Table 1.

Standard stock solution: 0.25 mg/mL of USP Desipramine Hydrochloride RS prepared as follows. Transfer a suitable quantity of USP Desipramine Hydrochloride RS to an appropriate volumetric flask, and add 50% of the final flask volume of Solution B. Sonicate for NLT 2 min, and allow the solution to equilibrate to room temperature. Dilute with Solution B to volume.

Standard solution: 0.005 mg/mL of USP Desipramine Hydrochloride RS from Standard stock solution in Solution B

System suitability solution: 0.01 mg/mL each of USP Imipramine Hydrochloride RS and USP Iminodibenzyl RS in Standard stock solution

Sensitivity solution: 0.3 µg/mL of USP Desipramine Hydrochloride RS from Standard solution in Solution B. Use within 24 h.

Sample solution: 0.5 mg/mL of Desipramine Hydrochloride prepared as follows. Transfer a suitable quantity of Desipramine Hydrochloride to an appropriate volumetric flask, and add 50% of the final flask volume of Solution B. Sonicate for NLT 2 min, and allow the solution to equilibrate to room temperature. Dilute with Solution B to volume.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 254 nm
• Column: 4.6-mm × 25-cm; 4-µm or 5-µm packing L1
• Column temperature: 60°
• Flow rate: 1.4 mL/min
• Injection volume: 40 µL

System suitability

• Samples: Standard solution, System suitability solution, and Sensitivity solution
• [Note-See Table 2 for relative retention times.]
• Suitability requirements:
• Resolution: NLT 2.0 between imipramine and iminodibenzyl, System suitability solution
• Signal-to-noise ratio: NLT 10, Sensitivity solution
• Relative standard deviation: NMT 3.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Desipramine Hydrochloride taken:

Result = (r_u/r_s) × (C_s/C_u) × (1/F) × 100

r_u = peak response of each impurity from the Sample solution

r_s = peak response of desipramine from the Standard solution

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

C_u = concentration of Desipramine Hydrochloride in the Sample solution (mg/mL)

F = relative response factor (see Table 2)

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

5 SPECIFIC TESTS

Loss on Drying 〈731〉

• Analysis: Dry under vacuum at 105° for 2 h.
• Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Protect from light.

USP Reference Standards 〈11〉

USP Desipramine Hydrochloride RS

USP Iminodibenzyl RS

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

C₁₄H₁₃N   195.28

USP Imipramine Hydrochloride RS