Verapamil 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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C₂₇H₃₈N₂O₄ · HCl 491.06

Benzeneacetonitrile, α-[3-[[2-(3,4-dimethoxyphenyl)ethyl]methylamino]propyl]-3,4-dimethoxy-α-(1-methylethyl)-, monohydrochloride, (±)-;

(±)-5-[(3,4-Dimethoxyphenethyl)methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile monohydrochloride CAS RN®: 152-11-4; UNII: V3888OEY5R.

1 DEFINITION

Verapamil Hydrochloride contains NLT 98.0% and NMT 102.0% of Verapamil Hydrochloride (C₂₇H₃₈N₂O₄ · HCl), calculated on the dried basis.

2 IDENTIFICATION

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

B. The retention time of the major peak for verapamil in the Sample solution corresponds to that of Standard solution B, as obtained in the test for Organic Impurities.

C. Identification Tests-General, Chloride 〈191〉: Meets the requirements

3 ASSAY

3.1 Procedure

Buffer: 1.23 g/L of sodium acetate containing about 33 mL/L of glacial acetic acid

Mobile phase: Acetonitrile, 2-aminoheptane, and Buffer (300:5:700)

Standard solution: 1 mg/mL of USP Verapamil Hydrochloride RS in Mobile phase

Sample solution: 1 mg/mL of Verapamil Hydrochloride in Mobile phase

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 278 nm
• Column: 4.6-mm × 15-cm; 5-µm packing L1
• Flow rate: 0.9 mL/min
• Injection volume: 10 µL
• Run time: NLT 2 times the retention time of verapamil

System suitability

• Sample: Standard solution
• Suitability requirements
• Tailing factor: NMT 2.0
• Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCl) in the portion of Verapamil Hydrochloride taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of verapamil from the Sample solution

rₛ = peak response of verapamil from the Standard solution

Cₛ = concentration of USP Verapamil Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = concentration of Verapamil 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%

Change to read:

4.2 Organic Impurities

Buffer and Mobile phase: Prepare as directed in the Assay.

System suitability solution: 1.9 mg/mL of USP Verapamil Hydrochloride RS and 1.5 mg/mL of USP Verapamil Related Compound B RS in Mobile phase

Standard solution A: 5.6 µg/mL of USP Verapamil Hydrochloride RS in Mobile phase

Standard solution B: 9.4 µg/mL of USP Verapamil Hydrochloride RS in Mobile phase

Sample solution: 1.9 mg/mL of Verapamil Hydrochloride in Mobile phase

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 278 nm
• Column: 4.6-mm × 12.5- to 15-cm; packing L1
• Flow rate: 0.9 mL/min
• Injection volume: 10 µL
• Run time: NLT 4 times the retention time of verapamil

System suitability

• Sample: System suitability solution
• [Note-The relative retention times for verapamil related compound B and verapamil are 0.88 and 1.0, respectively.]
• Suitability requirements
• Resolution: NLT 1.5 between the verapamil related compound B and verapamil peaks
• Relative standard deviation: NMT 2.0%

Analysis

Samples: Sample solution, Standard solution A, and Standard solution B

Acceptance criteria

Individual impurities: Any single peak response is not greater than that of the verapamil peak response from Standard solution A (0.3%).

Total impurities: The sum of the peak responses, other than that of verapamil, from the Sample solution is not greater than the verapamil peak response from Standard solution B (0.5%).

5 SPECIFIC TESTS

5.1 pH 〈791〉

Sample solution: 50 mg/mL. Prepare with gentle heating.

Acceptance criteria: 4.5–6.5

5.2 Loss on Drying 〈731〉

Analysis: Dry at 105° for 2 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Verapamil Hydrochloride RS

USP Verapamil Related Compound B RS

Benzeneacetonitrile, α-[2-[[2-(3,4-dimethoxyphenyl)-ethyl]methylamino]ethyl]-3,4-dimethoxy-α-(1-methylethyl)-, monohydrochloride.

C₂₆H₃₆N₂O₄ · HCl 477.05