Moexipril Hydrochloride

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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C₂₇H₃₄N₂O₇ · HCl 535.03

3-Isoquinolinecarboxylic acid, 2-[2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-1,2,3,4-tetrahydro-6,7-dimethoxy-, monohydrochloride, [3S-[2[R*(R*)],3R*]]-;

(3S)-2-[(2S)-N-[(1S)-1-Carboxy-3-phenylpropyl]alanyl]-1,2,3,4-tetrahydro-6,7-dimethoxy-3-isoquinolinecarboxylic acid, 2-ethyl ester, monohydrochloride CAS RN®: 82586-52-5  UNII: Q1UMG3UH45

1 DEFINITION

Moexipril Hydrochloride contains NLT 98.0% and NMT 102.0% of moexipril hydrochloride (C₂₇H₃₄N₂O₇ · HCl), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A.  Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

B. The relative 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〉, Chloride: Meets the requirements

3 ASSAY

3.1 Procedure

Buffer: 1.32 g/L of dibasic ammonium phosphate. Adjust with diluted phosphoric acid to a pH of 7.5.

Solution A: Acetonitrile and tetrahydrofuran (95:5)

Mobile phase: Solution A and Buffer (30:70)

Standard solution: 0.1 mg/mL of USP Moexipril Hydrochloride RS in Mobile phase. [Note-Sonication may be necessary for complete dissolution.]

Sample solution: 0.1 mg/mL of Moexipril Hydrochloride in Mobile phase. [Note-Sonication may be necessary for complete dissolution.]

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 215 nm
• Column: 4.6-mm × 25-cm; 5-µm packing L1
• Column temperature: 35°
• Flow rate: 1 mL/min
• Injection volume: 10 µL
• Run time: NLT 3.2 times the retention time of moexipril

System suitability

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of moexipril hydrochloride (C₂₇H₃₄N₂O₇ · HCl) in the portion of Moexipril Hydrochloride 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 = concentration of Moexipril Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the anhydrous basis

4 IMPURITIES

4.1 Residue on Ignition 〈281〉: NMT 0.20%

4.2 Organic Impurities

[Note-Use freshly prepared samples for analysis.]

Solution A and Chromatographic system: Proceed as directed in the Assay.

Solution B: Proceed as directed for the Buffer in the Assay.

Diluent: Solution A and Solution B (20:80)

Mobile phase: See Table 1.

Table 1

Standard solution 1: 4 µg/mL of USP Moexipril Hydrochloride RS in Diluent. [Note-Sonication may be necessary for complete dissolution.]

Standard solution 2: 2 mg/mL of USP Moexipril Hydrochloride RS and 3 µg/mL each of USP Moexipril Related Compound A RS, USP Moexipril Related Compound B RS, USP Moexipril Related Compound C RS, USP Moexipril Related Compound D RS, USP Moexipril Related Compound E RS, USP Moexipril Related Compound F RS, and USP Moexipril Related Compound G RS in Diluent. [Note-Sonication may be necessary for complete dissolution.]

Sample solution: 2 mg/mL of Moexipril Hydrochloride in Diluent. [Note-Sonication may be necessary for complete dissolution.]

System suitability

Samples: Standard solution 1 and Standard solution 2

Suitability requirements

Resolution: NLT 3.5 between moexipril related compound A and moexipril related compound E; NLT 2.5 between moexipril and moexipril related compound G, Standard solution 2

Relative standard deviation: NMT 5.0% for moexipril, Standard solution 1

Analysis

Samples: Standard solution 1, Standard solution 2, and Sample solution

Calculate the percentage of each specified impurity in the portion of Moexipril Hydrochloride taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of each specified impurity from the Sample solution

rₛ = peak response of the corresponding Reference Standard from Standard solution 2

Cₛ = concentration of each specified impurity in Standard solution 2 (mg/mL)

Cᵤ = concentration of Moexipril Hydrochloride in the Sample solution (mg/mL)

Calculate the percentage of any other individual unspecified impurity in the portion of Moexipril Hydrochloride taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of each individual unspecified impurity from the Sample solution

rₛ = peak response of moexipril from Standard solution 1

Cₛ = concentration of USP Moexipril Hydrochloride RS in Standard solution 1 (mg/mL)

Cᵤ = concentration of Moexipril Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. Disregard peaks less than 0.05%.

Table 2

ᵃ (S)-6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid.

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

ᶜ (S)-2-[(S)-1-Ethoxy-1-oxo-4-phenylbutan-2-ylamino]propanoic acid.

ᵈ (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.

ᵉ (S)-2-{(S)-2-[(S)-4-Cyclohexyl-1-ethoxy-1-oxobutan-2-ylamino]propanoyl}-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid.

ᶠ (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.

ᵍ (S)-tert-Butyl 2-{(S)-2-[(S)-1-ethoxy-1-oxo-4-phenylbutan-2-ylamino]propanoyl}-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate.

ʰ Sum of all specified and unspecified impurities.

4.3 Content of Imidazole

Mobile phase: Hexane, isopropyl alcohol, and diethyl amine (52:48:0.025)

Standard solution: 0.01 mg/mL of USP Imidazole RS in Mobile phase. [Note-Sonication may be necessary for complete dissolution.]

Sample solution: 2 mg/mL of Moexipril Hydrochloride in Mobile phase. [Note-Sonication may be necessary for complete dissolution. Use freshly prepared Sample solution for analysis.]

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 215 nm
• Column: 4.6-mm × 25-cm; 5-µm packing L3
• Flow rate: 1 mL/min
• Injection volume: 20 µL
• Run time: NLT 3.3 times the retention time of imidazole

System suitability

• Sample: Standard solution
• Suitability requirements
• Relative standard deviation: NMT 5.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of imidazole in the portion of Moexipril Hydrochloride taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of imidazole from the Sample solution

rₛ = peak response of imidazole from the Standard solution

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

Cᵤ = concentration of Moexipril Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: NMT 0.03%

5 SPECIFIC TESTS

Water Determination 〈921〉, Method I, Method Ia: NMT 1.5%

Optical Rotation 〈781S〉, Procedures, Specific Rotation

Sample solution: 0.011 g/mL of Moexipril Hydrochloride in alcohol.

Sonicate to dissolve the sample.

Acceptance criteria: +30.0° to +38.0°

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, protected from moisture. Store at room temperature.

USP Reference Standards 〈11〉

USP Imidazole RS

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 C RS

(S)-tert-Butyl 2-{(S)-2-[(S)-1-ethoxy-1-oxo-4-phenylbutan-2-ylamino]propanoyl}-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate.

C₃₁H₄₂N₂O₇ 554.67

USP Moexipril Related Compound D RS

(S)-2-{(S)-2-[(S)-4-Cyclohexyl-1-ethoxy-1-oxobutan-2-ylamino]propanoyl}-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid.

C₂₇H₄₀N₂O₇ 504.62

USP Moexipril Related Compound E RS

(S)-6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid.

C₁₂H₁₅NO₄ 237.25

USP Moexipril Related Compound F RS

(S)-2-[(S)-1-Ethoxy-1-oxo-4-phenylbutan-2-ylamino]propanoic acid.

C₁₅H₂₁NO₄ 279.33

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