Moexipril 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

Moexipril Hydrochloride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of moexipril hydrochloride (C₂₇H₃₄N₂O₇ · HCl).

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U

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

Buffer: 0.01 M potassium dihydrogen phosphate

Diluent: Acetonitrile and water (30:70)

Mobile phase: Acetonitrile and Buffer (350:650)

Standard solution: 0.075 mg/mL of USP Moexipril Hydrochloride RS in Diluent. Initially fill with Diluent to about 70% of the total volume, and sonicate. Further dilute with Diluent to volume.

Sample solution: Nominally 0.075 mg/mL of moexipril hydrochloride in Diluent, prepared from a suficient number of crushed Tablets as follows. Add Diluent to about 75% of the total volume, and sonicate for 30 min with intermittent shaking. Dilute with Diluent to volume, and pass through a suitable filter of 0.45-µm pore size.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 210 nm
• Column: 4.6-mm × 15-cm; 5-µm packing L7
• Column temperature: 45°
• Flow rate: 1.5 mL/min
• Injection volume: 20 µL
• Run time: 4 times the retention time of the moexipril peak

System suitability

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of moexipril hydrochloride (C₂₇H₃₄N₂O₇ · HCl) in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response from the Sample solution

rₛ = peak response from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

4.1 Dissolution 〈711〉

Test 1

Buffer, Diluent, Mobile phase, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Time: 15 min

Standard stock solution: 0.16 mg/mL of USP Moexipril Hydrochloride RS in Diluent. [Note-Sonication may be necessary for complete dissolution.]

Standard solution:

0.016 mg/mL of USP Moexipril Hydrochloride RS in Medium from the Standard stock solution for 15-mg Tablet strength and 0.008 mg/mL of USP Moexipril Hydrochloride RS in Medium from the Standard stock solution for 7.5-mg Tablet strength

Sample solution: Pass 10 mL of the solution under test through a suitable filter of 0.45-µm pore size, discarding the first 2–3 mL.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of moexipril hydrochloride (C₂₇H₃₄N₂O₇ · HCl) dissolved:

Result = (rᵤ/rₛ) × (C/L) × V × 100

rᵤ = peak response of moexipril from the Sample solution

rₛ = peak response of moexipril from the Standard solution

C = concentration of USP Moexipril Hydrochloride RS in the Standard solution

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

Tolerances: NLT 80% (Q) of the labeled amount of moexipril hydrochloride (C₂₇H₃₄N₂O₇ · HCl) is dissolved.

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

Buffer, Diluent, Mobile phase, Chromatographic system, and System suitability: Proceed as directed in the Assay.

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

Time: 30 min

Tolerances: NLT 80% (Q) of the labeled amount of moexipril hydrochloride (C₂₇H₃₄N₂O₇ · HCl) is dissolved.

4.2 Uniformity of Dosage Units 〈905〉 

Meet the requirements for Content Uniformity

5 IMPURITIES

5.1 Organic Impurities

Solution A: 0.025% trifiuoroacetic acid in water

Solution B: Acetonitrile and tetrahydrofuran (90:10)

Diluent: Acetonitrile and water (30:70)

Mobile phase: See Table 1.

Table 1

Impurity stock solution: 0.12 mg/mL of USP Moexipril Related Compound G RS in Diluent. [Note-Sonication may be necessary for complete dissolution.]

System suitability solution: 1.2 mg/mL of USP Moexipril Hydrochloride RS and 2.4 µg/mL of USP Moexipril Related Compound G RS from the Impurity stock solution in Diluent. [Note-Sonication may be necessary for complete dissolution.]

Standard stock solution: 1.2 mg/mL of USP Moexipril Hydrochloride RS in Diluent. Initially add Diluent to about 60% of the volume of the fiask, and sonicate with intermittent shaking for complete dissolution.

Standard solution: 6 µg/mL each of USP Moexipril Related Compound A RS and USP Moexipril Related Compound B RS, and 1.2 µg/mL of USP Moexipril Hydrochloride RS in Diluent from the Standard stock solution. [Note-Sonication may be necessary for complete dissolution.]

Sample solution: Nominally 1.2 mg/mL of moexipril hydrochloride in Diluent, prepared from a suficient number of crushed Tablets. Initially add Diluent to about 60% of the volume of the fiask, and sonicate for 20 min with intermittent shaking in ice cold water. Dilute with Diluent to volume. Pass through a suitable filter of 0.45-µm pore size.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 210 nm
• Column: 4.6-mm × 25-cm; 5-µm packing L1
• Column temperature: 30°
• Flow rate: 1 mL/min
• Injection volume: 10 µL

System suitability

• Samples: System suitability solution and Standard solution
• Suitability requirements
• Resolution: NLT 2.5 between moexipril and moexipril related compound G, System suitability solution
• Tailing factor: NMT 2.0 for the moexipril peak, System suitability solution
• Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: System suitability solution, Standard solution, and Sample solution

Calculate the percentage of moexipril related compound A and moexipril related compound B in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of moexipril related compound A and moexipril related compound B from the Sample solution

rₛ = peak response of moexipril related compound A and moexipril related compound B from the Standard solution

Cₛ = concentration of USP Moexipril Related Compound A RS and USP Moexipril Related Compound B RS in the Standard solution (mg/mL)

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

Calculate the percentage of any other individual unspecified degradation product in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of any other individual unspecified degradation product from the Sample solution

rₛ = peak response of moexipril from the Standard solution

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

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

Acceptance criteria: See Table 2. Disregard peaks less than 0.1%.

Table 2

ᵃ Process-related impurities controlled in the drug substance.

ᵇ (3S)-2-{(2S)-N-[(1S)-1-Carboxy-3-phenylpropyl]alanyl}-1,2,3,4-tetrahydro-6,7-dimethoxy-3-isoquinolinecarboxylic acid.

ᶜ (S)-Ethyl 2-{(3S,11aS)-8,9-dimethoxy-3-methyl-1,4-dioxo-3,4-dihydro-1H-pyrazino[1,2-b]isoquinolin-2(6H,11H,11aH)-yl}-4-phenylbutanoate.

ᵈ Total impurities do not include moexipril related compound A.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Store at controlled room temperature in tight, well-closed containers, and protect from moisture.

Labeling: When more than one Dissolution test is given, the labeling states the test used only if Test 1 is not used.

USP Reference Standards 〈11〉

USP Moexipril Hydrochloride RS

USP Moexipril Related Compound A RS

(3S)-2-{(2S)-N-[(1S)-1-Carboxy-3-phenylpropyl]alanyl}-1,2,3,4-tetrahydro-6,7-dimethoxy-3-isoquinolinecarboxylic acid.

C₂₅H₃₀N₂O₇ 470.51

USP Moexipril Related Compound B RS

(S)-Ethyl 2-{(3S,11aS)-8,9-dimethoxy-3-methyl-1,4-dioxo-3,4-dihydro-1H-pyrazino[1,2-b]isoquinolin-2(6H,11H,11aH)-yl}-4-phenylbutanoate.

C₂₇H₃₂N₂O₆ 480.55

USP Moexipril Related Compound G RS

(S)-6,7-Dimethoxy-2-{(S)-2-[(S)-1-methoxy-1-oxo-4-phenylbutan-2-ylamino]propanoyl}-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid.

C₂₆H₃₂N₂O₇ 484.54