Verapamil Hydrochloride Extended-Release Capsules

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

Verapamil Hydrochloride Extended-Release Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCI). 

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

PROCEDURE

Solution A: 0.01 N sodium acetate in water containing 33 mL/L of glacial acetic acid

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

System suitability solution: 0.12 mg/mL of USP Verapamil Hydrochloride RS and 0.1 mg/mL of USP Verapamil Related Compound B RS in Mobile phase

Standard solution: 0.12 mg/ml. of USP Verapamil Hydrochloride RS in Mobile phase

Sample stock solution: Nominally 1.2 mg/mL of verapamil hydrochloride prepared as follows. Transfer an equivalent to 240 mg of verapamil hydrochloride, from the pool of Capsule contents (NLT 20), to a 200-mL volumetric flask. Add about 150 mL of Mobile phase (prewarm the Mobile phase to 45°). While sonicating, stir for 1 h, cool to room temperature, dilute with Mobile phase to volume, and mix. Centrifuge a portion for 20 min, and use the supernatant.

Sample solution: Nominally 0.12 mg/mL of verapamil hydrochloride in Mobile phase from the Sample stock solution

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 278 nm. For Identification B, use a diode array detector in the range of 220-400 nm.

Column: 4.6-mm x 25-cm; 5-µm packing L1

Flow rate: 1.2 mL/min

Injection volume: 20 µL

Run time: NLT 2 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 0.84 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 1.5 between verapamil and verapamil related compound B, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCI) in the portion of Capsules taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of verapamil from the Sample solution 

r_S = peak response of verapamil from the Standard solution 

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

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

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

4.1.1 Test 1

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 100 rpm. Use a wire helix sinker as necessary.

Times: 2, 4, 8, and 24 h

Solution A, Mobile phase, and Chromatographic system: Proceed as directed in the Assay, except for the Injection volume.

Injection volume: 30 µL

System suitability solution: 0.25 mg/mL of USP Verapamil Hydrochloride RS and 0.2 mg/mL of USP Verapamil Related Compound B RS in Medium

Standard solution: 0.267 mg/mL of USP Verapamil Hydrochloride RS in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter.

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.5 between verapamil and verapamil related compound B, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of verapamil hydrochloride (CHNO HCI) dissolved at each time point (i):

                  Q₂ = (r_U/r_S) × (C_S/L) x V x 100

                  Q₄ = (Q₂ × V_S1/V) + [(r_U/r_S) × (C_S/L) × (V - V_S1) × 100] 

                  Q₈ = (Q₂ × V_S1/V) + {Q₄ × V_S2/ [V - (V_S1 + V_S2)]} + ((r_U/r_S) x (C_S/L) x (V - (V_S1 + V_S2)] ×100}

                  Q₂₄ = (Q₂ x V_S1/V) + {Q₄ x × V_S2/ [V - (V_S1 +V_S2)]} + {Q8 x V_S3/ [V - (V_S1 + V_S2 + V_S3)]} + {(r_U/r_S) x  (C_S/L) x [V - (V_S1 + V_S2 + V_S3)] ×100}

r_U = peak response of verapamil from the Sample solution r_{u} = 1

r_S = peak response of verapamil from the Standard solution

C_S = concentration of USP Verapamil Hydrochloride RS in the Standard solution C

L = label claim (mg/Capsule)

V = initial volume of Medium, 900 mL

V_Si = volume of Medium taken at each time point (mL)

Tolerances: See Table 1.

Table 1

The percentages of the labeled amount of verapamil hydrochloride (C₂₇H₃₈N₂O₄ · HCI) released at the times specified conform to Dissolution (711), Acceptance Table 2.

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

Medium, Apparatus 2, Times, Solution A, Mobile phase, System suitability solution, Standard solution, Sample solution, Chromatographic system, System suitability, and Analysis: Proceed as directed in Test 1.

Tolerances: See Table 2.

Table 2

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

ORGANIC IMPURITIES

Solution A, Mobile phase, and Sample stock solution: Prepare as directed in the Assay.

System suitability solution: 6 µg/mL of USP Verapamil Hydrochloride RS and 4.8 µg/mL of USP Verapamil Related Compound B. RS in Mobile phase

Standard solution: 6 µg/mL of USP Verapamil Hydrochloride RS in Mobile phase

Sample solution: Use the Sample stock solution.

Chromatographic system: Proceed as directed in the Assay, except for the Injection volume and Run time.

Injection volume: 50 µL

Run time: NLT 5 times the retention time of verapamil

System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 3 for relative retention times.]

Suitability requirements

Resolution: NLT 1.5 between verapamil and verapamil related compound B, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each unspecified degradation product in the portion of Capsules taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each unspecified degradation product from the Sample solution 

r_S = peak response of verapamil from the Standard solution

C_S = concentration of USP Verapamil Hydrochloride RS in the Standard solution (µg/mL)

C_U = nominal concentration of verapamil hydrochloride in the Sample solution(µg/ml.)

Acceptance criteria: See Table 3.

Table 3

^a For resolution measurement only. Do not include it in the total.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers. Store at controlled room temperature.

LABELING: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 7 is not used.

USP REFERENCE STANDARDS (11)

USP Verapamil Hydrochloride RS

USP Verapamil Related Compound B. RS

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

C₂₆H₃₆N₂O₄ · HCI            477.05