Verapamil Hydrochloride Injection

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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1 DEFINITION

Verapamil Hydrochloride Injection is a sterile solution of Verapamil Hydrochloride in Water for Injection. It contains NLT 90.0% and NMT 110.0% of the labeled amount of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCl).

2 IDENTIFICATION

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A. The UV spectrum of the major peak of the Diluted sample solution corresponds to that of the Diluted standard solution, as obtained in the Assay.

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 〈191〉, Chemical Identification Tests, Chloride: Meets the requirements

3 ASSAY

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3.1 Procedure

Solution A: 0.015 N sodium acetate solution containing 33 mL of glacial acetic acid per liter

Mobile phase: Acetonitrile, Solution A, and 2-aminoheptane (30:70:0.5)

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: 2.5 mg/mL of USP Verapamil Hydrochloride RS in Mobile phase

Diluted standard solution: 0.5 mg/mL of USP Verapamil Hydrochloride RS from the Standard solution in Mobile phase

Sample solution: Nominally 2.5 mg/mL of verapamil hydrochloride from a volume of Injection in Mobile phase

Diluted sample solution: Nominally 0.5 mg/mL of verapamil hydrochloride from the Sample solution in Mobile phase

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 278 nm. For Identification A, use a diode array detector in the range of 200–400 nm.
• Column: 4.6-mm × 15-cm; 5-µm packing L1
• Flow rate: 0.9 mL/min
• Injection volume: 10 µL
• Run time: NLT 4 times the retention time of verapamil

System suitability

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

Analysis

Samples: Standard solution, Diluted standard solution, Sample solution, and Diluted sample solution

[Note-The Diluted standard solution and Diluted sample solution are used for Identification A.]

Calculate the percentage of the labeled amount of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCl) in the volume of Injection 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 = nominal concentration of verapamil hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

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4.1 Organic Impurities

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

Standard solution: 2.5 mg/mL of USP Verapamil Hydrochloride RS, and 7.5 µg/mL each of USP Verapamil Related Compound A RS, USP Verapamil Related Compound E RS, and USP Verapamil Related Compound F RS in Mobile phase

System suitability

• Samples: System suitability solution and Standard solution
• [Note-See Table 1 for relative retention times.]
• Suitability requirements
• Resolution: NLT 1.5 between verapamil related compound B and verapamil, System suitability solution
• Relative standard deviation: NMT 2.0%, Standard solution
• Signal-to-noise ratio: NLT 15 for verapamil related compound F, Standard solution

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of each specified degradation product in the portion of Injection taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of verapamil related compound A, E, or F from the Sample solution

rₛ = peak response of verapamil related compound A, E, or F from the Standard solution

Cₛ = concentration of USP Verapamil Related Compound A RS, USP Verapamil Related Compound E RS, or USP Verapamil Related Compound F RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of verapamil hydrochloride in the Sample solution (mg/mL)

Calculate the percentage of any unspecified degradation product in the portion of Injection taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of any unspecified degradation product 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 = nominal concentration of verapamil hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: See Table 1.

Table 1

ᵃ For resolution measurement only. It is not to be reported and not to be included in the total degradation products.

5 SPECIFIC TESTS

pH 〈791〉: 4.0–6.5

Bacterial Endotoxins Test 〈85〉: NMT 16.7 USP Endotoxin Units/mg of verapamil hydrochloride

Particulate Matter in Injections 〈788〉: Meets the requirements for small-volume injections

Other Requirements: Meets the requirements in Injections and Implanted Drug Products 〈1〉

6 ADDITIONAL REQUIREMENTS

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Packaging and Storage: Preserve in single-dose containers, preferably of Type I glass, protected from light. Store at controlled room temperature.

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USP Reference Standards 〈11〉

USP Verapamil Hydrochloride RS

USP Verapamil Related Compound A RS

2-(3,4-Dimethoxyphenyl)-2-isopropyl-5-(methylamino)pentanenitrile hydrochloride.

C₁₇H₂₆N₂O₂ · HCl 326.87

USP Verapamil Related Compound B RS

4-[(3,4-Dimethoxyphenethyl)(methyl)amino]-2-(3,4-dimethoxyphenyl)-2-isopropylbutanenitrile hydrochloride.

C₂₆H₃₆N₂O₄ · HCl 477.04

USP Verapamil Related Compound E RS

3,4-Dimethoxybenzaldehyde.

C₉H₁₀O₃ 166.17

USP Verapamil Related Compound F RS

(3,4-Dimethoxyphenyl)methanol.

C₉H₁₂O₃ 168.19