Desipramine 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)

DOWNLOAD PDF HERE

1 DEFINITION

Desipramine Hydrochloride Tablets contain NLT 95.0% and NMT 105.0% of the labeled amount of desipramine hydrochloride (C₁₈H₂₂N₂·HCl).

2 IDENTIFICATION

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

B. The UV spectrum 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

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

Mobile phase: Acetonitrile, methanol, and Buffer (30:20:50)

Diluent: 0.1 N 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: 0.02 mg/mL of USP Desipramine Hydrochloride RS in Diluent. Sonication may be used to promote dissolution.

Sample stock solution: Nominally 1–1.5 mg/mL of desipramine hydrochloride from Tablets prepared as follows. Transfer NLT 20 Tablets into a suitable volumetric flask. Add 50% of the final flask volume of Diluent. Sonicate the flask for NLT 15 min. Shake the flask for NLT 15 min. Dilute with Diluent to volume.

Sample solution: Nominally 0.02 mg/mL of desipramine hydrochloride prepared as follows. Transfer a suitable volume of Sample stock solution to an appropriate volumetric flask. Add 50% of the final flask volume of Diluent. Shake the flask for NLT 5 min and dilute with Diluent to volume. Pass through a suitable filter and discard the first 5 mL of the filtrate.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 250 nm. For Identification B, use a diode array detector in the range of 200–400 nm.
• Column: 4.6-mm × 25-cm; 5-µm packing L10
• Flow rate: 1.5–2.0 mL/min
• Injection volume: 25 µL
• Run time: NLT 1.2 times the retention time of the imipramine peak

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 1.5, Standard solution
• Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of desipramine hydrochloride (C₁₈H₂₂N₂·HCl) 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

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

C_u = nominal concentration of desipramine hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 95.0%–105.0%

4 PERFORMANCE TESTS

4.1 Dissolution 〈711〉

4.1.1 Test 1

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 60 min

Standard solution: USP Desipramine Hydrochloride RS in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter. If necessary, dilute with Medium to a concentration that is similar to that of the Standard solution.

Instrumental conditions

• Mode: UV
• Analytical wavelength: Maximum absorbance at 251 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of desipramine hydrochloride (C₁₈H₂₂N₂·HCl) dissolved:

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

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of USP Desipramine 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 desipramine hydrochloride (C₁₈H₂₂N₂·HCl) is dissolved.

4.1.2 Test 2 If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Medium: 0.1 N hydrochloric acid; 900 mL, deaerated

Apparatus 2: 50 rpm

Time:

• For Tablets labeled to contain 10, 25, 50, or 75 mg: 15 min
• For Tablets labeled to contain 100 or 150 mg: 30 min

Buffer: Dissolve 2.72 g monobasic potassium phosphate in 1 L water and sonicate. Add 8.0 mL triethylamine. Adjust with phosphoric acid to pH 3.0.

Mobile phase: Methanol and Buffer (65:35)

Standard stock solution: 0.555 mg/mL of USP Desipramine Hydrochloride RS prepared as follows. Transfer a suitable amount of USP Desipramine Hydrochloride RS to an appropriate volumetric flask. Add 10% of the flask volume of methanol and sonicate to dissolve.

Dilute with Medium to volume.

Standard solution: (L/900) mg/mL of USP Desipramine Hydrochloride RS from Standard stock solution, in Medium, where L is the label claim in mg/Tablet

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.

Chromatographic system

• (See Chromatography (621). System Suitability.)
• Mode: LC
• Detector: UV 251 nm
• Column: 4.6-mm x 15-cm; 5-µm packing 11
• Column temperature: 45"
• Flow rate: 1 mL/min
• Injection volume: 10 µL
• Run time: NLT 1.5 times the retention time of desipramine

System suitability

• Sample: Standard solution
• Suitability requirements
• Tailing factor: NMT 2.0
• Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of desipramine hydrochloride (C₁₈H₂₂N₂·HCl) dissolved:

Result = (r_u/r_s) × C_s × V × (1/L) × 100

r_u = peak response of desipramine 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)

V = volume of the Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of desipramine hydrochloride (CHN, HCI) is dissolved (RB 1-Jan-2022)

4.2 UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

5 IMPURITIES

5.1 ORGANIC IMPURITIES

Buffer: 5.2 g/L of dibasic potassium phosphate in water. To each L of solution, add 1 mL of triethylamine 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. Add 50% of the final flask volume of Solution B. Sonicate for NLT 2 min. 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: Norninally 0.5 mg/mL of desipramine hydrochloride from Tablets prepared as follows. Finely powder NLT 20 Tablets. Transfer a suitable portion of this powder, equivalent to 50 mg of desipramine hydrochloride, to a 100-ml volumetric flask with the aid of Solution B. Add Solution B to about 50% of the flask volume, and sonicate the flask with occasional shaking for NLT 10 min. Allow the solution to equilibrate to room temperature. Dilute with Solution B to volume. Pass through a suitable filter, and discard NLT the first 2 mL of filtrate.

Chromatographic system

• (See Chromatography (621), System Suitability.)
• Mode: LC
• Detector: UV 254 nm
• Column: 4.6-mm x 25-cm; 4-µm or 5-um packing 11
• 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
• Relative standard deviation: NMT 3.0%, Standard solution
• Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

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

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

r_u = peak response of each degradation product 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 = nominal 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%.

6 ADDITIONAL REQUIREMENTS

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

Add the following:

Labeling: When more than one Dissolution Test is given, labeling states test used only if Test 1 is not used.

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