Clomipramine Hydrochloride

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

C₁₉H₂₃ClN₂·HCl 351.31

5H-Dibenz[b,f]azepine-5-propanamine, 3-chloro-10,11-dihydro-N,N-dimethyl-, monohydrochloride;

3-Chloro-5-[3-(dimethylamino)propyl]-10,11-dihydro-5H-dibenz[b,f]azepine monohydrochloride

CAS RN®: 17321-77-6; UNII: 2LXW0L6GWJ.

1 DEFINITION

Clomipramine Hydrochloride contains NLT 98.0% and NMT 102.0% of clomipramine hydrochloride (C₁₉H₂₃ClN₂·HCl), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

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

Change to read:

2.2 B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U

Medium: 0.1 N hydrochloric acid

Solution: 100 µg/mL

Acceptance criteria: Absorptivities, calculated on the dried basis, do not differ by more than 1.0% at the wavelength of maximum absorbance.

3 ASSAY

3.1 Procedure

Solution A: 55 g/L of sodium 1-heptanesulfonate prepared as follows. Transfer a suitable quantity of sodium 1-heptanesulfonate to an appropriate volumetric flask. Dissolve in 50% of the flask volume of water, and dilute with glacial acetic acid to volume.

Mobile phase: Transfer 20.0 mL of Solution A and 2.0 mL of triethylamine to a 500-mL volumetric flask, and dilute with water to volume. Transfer this solution to a 1-L volumetric flask, adjust with phosphoric acid to a pH of 3.2 ± 0.1, dilute with acetonitrile to volume, filter, and degas.

System suitability solution: 0.07 mg/mL of USP Desipramine Hydrochloride RS and 0.10 mg/mL of USP Imipramine Hydrochloride RS in methanol

Standard solution: 0.32 mg/mL of USP Clomipramine Hydrochloride RS in methanol

Sample solution: 0.32 mg/mL of Clomipramine Hydrochloride in methanol

Chromatographic system

• (See Chromatography <621>, System Suitability.)
• Mode: LC
• Detector: UV 254 nm
• Column: 3.9-mm × 30-cm; packing L1
• Flow rate: 1 mL/min
• Injection volume: 10 µL

System suitability

• Sample: System suitability solution
• [Note-The relative retention times for desipramine and imipramine are 0.85 and 1.0, respectively.]
• Suitability requirements
• Resolution: NLT 0.5 between desipramine and imipramine
• Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of clomipramine hydrochloride (C₁₉H₂₃ClN₂·HCl) in the portion of Clomipramine 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 Clomipramine Hydrochloride RS in the Standard solution (mg/mL)

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

Acceptance criteria: 98.0%-102.0% on the dried basis

4 IMPURITIES

4.1 Residue on Ignition 〈281〉: NMT 0.1%

4.2 Organic Impurities, Procedure 1

Solution A and System suitability solution: Proceed as directed in the Assay.

Mobile phase: Transfer 20.0 mL of Solution A, 2.0 mL of triethylamine, and 500 mL of water to a suitable container. Adjust with phosphoric acid to a pH of 3.2 ± 0.1, and dilute with water to 625 mL. Transfer to a 1-L volumetric flask, and dilute with acetonitrile to volume.

Sample solution: 2 mg/mL of Clomipramine Hydrochloride in methanol

Chromatographic system and System suitability: Proceed as directed in the Assay, except use an Injection volume of 5 µL.

Analysis

Sample: Sample solution

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

Result = (r_u/r_T) × 100

r_u = peak response of each impurity

r_T = sum of all the peak responses

Acceptance criteria: See Table 1.

4.3 Organic Impurities, Procedure 2

Solution A, Mobile phase, System suitability solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Sample solution: 2 mg/mL of Clomipramine Hydrochloride in methanol

Analysis

Sample: Sample solution

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

Result = (r_u/r_T) × 100

r_u = peak response of each impurity

r_T = sum of the responses of all the peaks

Acceptance criteria: See Table 1.

a Sum of all impurities from Organic Impurities, Procedure 1 and Organic Impurities, Procedure 2.

5 SPECIFIC TESTS

5.1 pH 〈791〉

Sample solution: 100 mg/mL of Clomipramine Hydrochloride in water

Acceptance criteria: 3.5–5.0

5.2 Loss on Drying 〈731〉

Analysis: Dry at 105° for 2 h.

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

6.1 Packaging and Storage

Preserve in well-closed containers.

6.2 USP Reference Standards 〈11〉

USP Clomipramine Hydrochloride RS

USP Desipramine Hydrochloride RS

USP Imipramine Hydrochloride RS