Amlodipine and Benazepril Hydrochloride Capsules

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

Amlodipine and Benazepril Hydrochloride Capsules contain an amount of amlodipine besylate equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of amlodipine (C₂₀H₂₅CIN₂O₅) and NLT 90.0% and NMT 110.0% of the labeled amount of benazepril hydrochloride (C₂₄H₂₈N₂O₅·HCI).

2 IDENTIFICATION

A. The retention times of the major peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay

B. The UV spectra of the major peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay.

3 ASSAY

Change to read:

3.1 PROCEDURE

Buffer 1: 0.7% (v/v) triethylamine in water. Adjust with phosphoric acid to a pH of 3.0, and add 1.2 g/L of tetrabutylammonium (ERR-1-Oct-2024) hydrogen sulfate to this solution.

Buffer 2: 0.7% (v/v) triethylamine in water. Adjust with phosphoric acid to a pH of 3.0.

Mobile phase: Acetonitrile, methanol, and Buffer 1 (10:30:70)

Diluent: Acetonitrile, methanol, and Buffer 2 (20:30:50)

Standard solution: Concentrations of USP Amlodipine Besylate RS and USP Benazepril Hydrochloride RS in Diluent as directed in Table 1.

Table 1

Sample solution: Transfer the contents of 5 Capsules into a suitable volumetric flask to obtain nominal concentrations as given in Table 2. Add Diluent to about 70% of the volume of the flask and keep on a rotary shaker for about 45 min, sonicate for about 30 min with occasional shaking, and dilute with Diluent to volume. Centrifuge a portion of the solution for about 10 min, and pass through a filter of 0.45-µm pore size.

Table 2

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 237 nm. For Identification B, use a diode array detector in the range of 200-400 nm.

Column: 4.6-mm x 15-cm; 5-µm packing L1

Flow rate: 1.2 mL/min

Injection volume: 10 µL

Run time: NLT 2 times the retention time of amlodipine

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0 for the amlodipine and benazepril peaks

Relative standard deviation: NMT 2.0% for the amlodipine and benazepril peaks

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of amlodipine (C₂₀H₂₅CIN₂O₅) in the portion of Capsules taken:

Result = (r_U/r_S) x (C_S/C_U) x (M_r1/M_r2) x 100

r_U = peak response of amlodipine from the Sample solution

r_S = peak response of amlodipine from the Standard solution s

C_S = concentration of USP Amlodipine Besylate RS in the Standard solution (mg/mL)

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

M_r1 = molecular weight of amlodipine, 408.88

M_r2 = molecular weight of amlodipine besylate, 567.05

Calculate the percentage of the labeled amount of benazepril hydrochloride (C₂₄H₂₈N₂O₅·HCI), in the portion of Capsules taken:

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

r_U = peak response of benazepril from the Sample solution

r_S = peak response of benazepril from the Standard solution

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

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

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

Medium: 0.01 N hydrochloric acid: 500 mL

Apparatus 1: 100 rpm

Time: 30 min

Buffer: 2.72 g/L of potassium phosphate, monobasic in water. Add 0.2% (v/v) triethylamine per liter. Adjust with phosphoric acid to a pH of 3.0.

Mobile phase: Acetonitrile, methanol, and Buffer (15:35:50)

Standard solution: Concentrations of USP Amlodipine Besylate RS and USP Benazepril Hydrochloride RS in Medium prepared as directed in Table 3.

Table 3

Chromatographic system

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

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 237 nm

Column: 4.6-mm x 10-cm; 3-µm packing L1

Flow rate: 1 mL/min

Injection volume: 50 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0 for the amlodipine and benazepril peaks

Relative standard deviation: NMT 2.0% for the amlodipine and benazepril peaks

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of amlodipine (C₂₀H₂₅CIN₂O₅) dissolved:

Result = (r_U/r_S) x (C_S/L) x (M_r1/M_r2) x V x 100

r_U = peak response of amlodipine from the Sample solution

r_S = peak response of amlodipine from the Standard solution

C_S = concentration of USP Amlodipine Besylate RS in the Standard solution (mg/mL)

L = label claim (mg/Capsule)

M_r1 = molecular weight of amlodipine, 408.88

M_r2 = molecular weight of amlodipine besylate, 567.05

V = volume of Medium, 500 mL

Calculate the percentage of the labeled amount of benazepril hydrochloride (C₂₄H₂₈N₂O₅·HCI) dissolved:

Result = (r_U/r_S) x (C_S/L) x V x 100

r_U = peak response of benazepril from the Sample solution

r_S = peak response of benazepril from the Standard solution

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

L = label claim (mg/Capsule)

V = volume of Medium, 500 mL

Tolerances: NLT 80% (Q) of the labeled amount of amlodipine (C₂₀H₂₅CIN₂O₅) and benazepril hydrochloride (C₂₄H₂₈N₂O₅·HCI) is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

ORGANIC IMPURITIES

Buffer 1, Buffer 2, and Diluent: Prepare as directed in the Assay.

Solution A: Acetonitrile and Buffer 1 (20:80)

Solution B: Methanol and Buffer 1 (80:20)

Mobile phase: See Table 4.

Table 4

Standard solution: 1 µg/mL each of USP Amlodipine Besylate RS and USP Amlodipine Related Compound A RS and 3 µg/mL each of USP Benazepril Hydrochloride RS and USP Benazepril Related Compound C RS in Diluent

Sample solution: Nominally 0.25 mg/mL of amlodipine in Diluent prepared as follows. Transfer a portion of the finely powdered contents of Capsules (NLT 20), equivalent to 25 mg of amlodipine, to a 100-mL volumetric flask. Add Diluent, about 70% of the volume of the flask, sonicate for 30 min with intermittent shaking, and dilute with Diluent to volume. Pass through a membrane filter of 0.45-um pore size. [NOTE -The benazepril hydrochloride concentration may vary depending on the ratio of amlodipine to benazepril hydrochloride in the Capsule.]

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 237 nm

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

Column temperature: 40°

Flow rate: 1.2 mL/min

Injection volume: 40 µL

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 2.0 between the amlodipine and benazepril peaks

Tailing factor: NMT 2.0 for the amlodipine and benazepril peaks

Relative standard deviation: NMT 5.0% for the amlodipine, amlodipine related compound A, benazepril, and benazepril related compound C peaks

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of amlodipine related compound A (free base) in the portion of Capsules taken:

Result = (r_U/r_S) x (C_S/C_U) x (M_r1/M_r2) x 100

r_U = peak response of amlodipine related compound A from the Sample solution

r_S = peak response of amlodipine related compound A from the Standard solution

C_S = concentration of USP Amlodipine Related Compound A RS in the Standard solution (mg/mL)

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

M_r1 = molecular weight of amlodipine related compound A (free base), 408.88

M_r2 = molecular weight of amlodipine related compound A, 522.94

Calculate the percentage of benazepril related compound C in the portion of Capsules taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of benazepril related compound C from the Sample solution

r_S = peak response of benazepril related compound C from the Standard solution s

C_S = concentration of USP Benazepril Related Compound C RS in the Standard solution (mg/mL)

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

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

Result = (r_U/r_T) x 100

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

r_T = sum of responses of all peaks from the Sample solution

Acceptance criteria: See Table 5. [NOTE-Disregard the peaks at relative retention times of 0.09 and 0.10.]

Table 5

^a 3-Ethyl 5-methyl [2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-3,5-pyridinedicarboxylate].

^b Sum of all degradation products exclude process related impurities.

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in well-closed containers, and store at controlled room temperature.

6.2 USP REFERENCE STANDARDS (11)

USP Amlodipine Besylate RS

USP Amlodipine Related Compound A RS

3-Ethyl 5-methyl [2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-3,5-pyridinedicarboxylate] fumarate.

C₂₀H₂₃CIN₂O₅·C₄H₄O₄ 522.94

USP Benazepril Hydrochloride RS

USP Benazepril Related Compound C. RS

(3S)-3-[[(1S)-1-Carboxy-3-phenylpropyl]amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benazepine)-1-acetic acid;

Also known as (S)-2-{[(S)-1-(Carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-yl)amino)-4-phenylbutanoic acid.

C₂₀H₂₄N₂O₅ 396.44