Benazepril Hydrochloride Tablets

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

Benazepril Hydrochloride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of benazepril hydrochloride (C₂₄H₂₈N₂O₅ . HCI).

2 IDENTIFICATION

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the 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.

3 ASSAY

3.1 PROCEDURE

Solution A: Dissolve 0.81 g of tetrabutylammonium bromide in 360 mL of water containing 0.2 mL of acetic acid, glacial.

Mobile phase: Methanol and Solution A (64:36)

System suitability solution: 0.4 mg/mL each of USP Benazepril Hydrochloride RS and USP Benazepril Related Compound B RS in Mobile phase

Standard solution: 0.2 mg/mL of USP Benazepril Hydrochloride RS in Mobile phase

Sample solution: Nominally 0.2 mg/mL of benazepril hydrochloride in Mobile phase prepared as follows. Transfer a portion from NLT 20 finely powdered Tablets, equivalent to 50 mg of benazepril hydrochloride, to a 250-mL volumetric flask. Add 150 mL of Mobile phase, and shake by mechanical means for 30 min. Dilute with Mobile phase to volume, mix, and centrifuge. Pass an aliquot of the supernatant through a suitable filter, discarding the first 6 mL of the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 240 nm. For Identification A, use a diode array detector in the range of 200-400 nm.

Columns

Guard: 4.6-mm x 3-cm; 7-µm packing L7

Analytical: 3.9-mm × 30-cm; 10-µm packing L1

Flow rate: 1 mL/min

Injection volume: 25 µL

Run time: NLT 3 times the retention time of benazepril

System suitability

Sample: System suitability solution

[NOTE-The relative retention times for benazepril and benazepril related compound B peaks are about 1.0 and 1.5, respectively.]

Suitability requirements

Resolution: NLT 2.0 between benazepril and benazepril related compound B peaks

Relative standard deviation: NMT 2.0% for both benazepril and benazepril related compound B peaks

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of benazepril hydrochloride (C₂₄H₂₈N₂O₅ . HCI) in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 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)

Test 1

Medium: Water; 500 mL

Apparatus 2: 50 rpm

Time: 30 min

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

Standard solution: 0.02 µg/µL of USP Benazepril Hydrochloride RS in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter. [NOTE-The amount of benazepril injected should not

exceed 125% of the quantity of the Standard solution (1.5 µg).]

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

Injection volume: 25 µL for System suitability solution; 60 µL for Standard solution and Sample solution

Analysis

Samples: Standard solution and Sample solution

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

Result = (r_U/r_S) × (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 s

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

L = label claim (mg/Tablet)

V = volume of Medium, 500 mL

Tolerances: NLT 80% (Q) of the labeled amount of benazepril hydrochloride (C24H28N2O5, HCI) is dissolved.

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

Medium, Apparatus 2, Standard solution, Sample solution, Chromatographic system, and Analysis: Proceed as directed in Dissolution Test 1.

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

Time: 45 min

Tolerances: NLT 70% (Q) of the labeled amount of benazepril hydrochloride (C24H28N2O5 HCI) is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

5.1 ORGANIC IMPURITIES

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

Standard solution: 0.006 mg/mL of USP Benazepril Related Compound C RS in Mobile phase

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

Injection volume: 25 µL for System suitability solution; 80 µL for Standard solution and Sample solution

Analysis

Samples: Sample solution and Standard solution

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

Result = (r_U/r_S) × (C_S/C_U) × 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

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 impurity in the portion of Tablets taken:

Result = (r_U/r_T) × 100

r_U = peak response of each impurity from the Sample solution

r_T = sum of the responses of all the peaks including benazepril related compound C from the Sample solution

Acceptance criteria: See Table 1.

Table 1

^a 2-[(SR)-3-{[(RS)-1-Ethoxy-1-oxo-4-phenylbutan-2-yl]amino)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl]acetic acid.

^b For identification only.

^c Excluding benazepril related compound C.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed 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 1 is not used.

Change to read:

USP REFERENCE STANDARDS (11)

USP Benazepril Hydrochloride RS

USP Benazepril Related Compound B RS

2-[(S)-3-([(R)-1-Ethoxy-1-oxo-4-phenylbutan-2-yl]amino)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl]acetic acid hydrochloride;

Also known as (ERR 1-Jul-2021) (3S)-3-[(1R)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetic acid, monohydrochloride.

C₂₄H₂₈N₂O₅ . HCI  460.95

USP Benazepril Related Compound C RS

(3S)-3-[[(1S)-1-Carboxy-3-phenylpropyl] amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine]-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.

C₂₂H₂₄N₂O₅  396.44