Enalapril Maleate

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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l-Proline, 1-[N-[1-(ethoxycarbonyl)-3-phenylpropyl]-l-alanyl]-, (S)-, (Z)-2-butenedioate (1:1);

1-[N-[(S)-1-Carboxy-3-phenylpropyl]-l-alanyl]-l-proline, 1′-ethyl ester, maleate (1:1) CAS RN^®: 76095-16-4; UNII: 9O25354EPJ.

1 DEFINITION

Enalapril Maleate contains NLT 98.0% and NMT 102.0% of enalapril maleate (C₂₀H₂₈N₂O₅ · C₄H₄O₄) calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A .SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: (197M) or (197A)

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

Change to read:

PROCEDURE

Buffer 1: 2.8 g of sodium phosphate, monobasic in 900 ml. of water in a 1000-ml volumetric flask. Adjust with a 9 M sodium hydroxide A

Buffer 2: 2.8 g of sodium phosphate, monobasic in 900 ml of water in a 1000-mL volumetric flask. Adjust with phosphoric acid to a pH of (USP 1-Dec-2019) 2.5, and dilute with water to volume.

Solution A: Acetonitrile and Buffer 7 (5:95)

Solution B: Acetonitrile and Buffer 1 (66:34)

Mobile phase: See Table 1

Diluent: Acetonitrile and Buffer 2 (5.95)

Standard solution: 0.3 mg/ml of USP Enalapril Maleate RS in Diluent

Sample solution: 0.3 mg/ml. of Enalapril Maleate in Diluent

Chromatographic system (See Chromatography (621) System Suitability)

Mode: LC

Detector: sqrt(215nm)

Columns: 4.1mm x 15cm packing L

Column temperature: 70°

Flow rate: 1.5 l/min

Injection volume: 50

System suitability

Sample: Standard solution 1 De-201

Suitability requirements

*Talling factor: NMT 2.0 

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standardson and Sample solution

Calculate the percentage of enalapril maleate (C₂₀H₂₈N₂O₅ · C₄H₄O₄) in the portion of Enalapril Maleste taken

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

r_U = peak response of enalapril from the Sample solution

r_S = peak response of enalapril from the Standard solution

C_S = concentration of USP Enalapril Maleate RS in the Standard solution (mg/ml)

C_U = concentration of Enalapril Maleate in the Sample solution (mg/ml)

Acceptance criteria: 98.0%-102.01% on the dead basis

4 IMPURITIES

Residue on Ignition (281): NMT 0.2%

Change to read

Buffer: 0.14 g/l, of notassum choentate mensbasis in wates Adjust with abouabionic acid to a pH of 2.0

Solution A Acetustzile and Buffer (1090)

Solution B: Acetonitrile and Buffer (80:20)

Mobile phase: See Table 2

Diluent Acctuntile and Buffer (20:80)

System suitability solution: 1 mg/m of USP Enalapril Maleate RS and 3 ugimi of USP Moexpril Related Compound F-RG in Diluent, Sonicate to dissolve as needed.

Standard solution: 0.01 mg/mL of USP Enalapril Maleate RS in Diluent

Sensitivity solution: 0.5 µg/m of USP Enalapril Maleate RS in Ditwns from the Standard solution

Sample solution: 1 mg/ml, of Enalapril Maleate in Diluent Sonicate to dissolve an needed.

Chromatographic system

(See Shamayanti Sotem Sul)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm × 25-cm; 5-μm packing L7

Temperatures

Autocampler: 20°

Colume 70°

Flew rate: 1.5 mL/min

Injection volume: 50 μL

System suitability

Samples: System suitability solution, Standard solution, and Senalivity anlution

No-See Table for the relative retention times

Sultability requirements

Resolution: LT 1.0 between monsipil related compound and enalapril System suttatality anlation

Tailing factor: NMT 2.0 Standant sution

Relative standard deviation: NMT 5.0%, Standard soun

Signal-to-noise ratio: NLT 10. Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of of Enalapril Maleate taken:

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

r_U = peak response of Enalapril Maleate from the Sample solution

r_S = peak response of Enalapril Maleate from the Standard solution

C_S = concentration of USP Enalapril Maleate RS in the Standard solution (mg/ml)

C_U = concentration of Enalapril Maleate in the Sample solution (mg/mL)

F = relative response factor (see Table 3)

Acceptance criteria: See Table 3. The reporting threshold is 0.05%.

^a This peak is due to the counterion and is not to be reported or included in the total impurities.

^b 1-[N-[(S)-1-Carboxy-3-phenylpropyl]-l-alanyl]-l-proline.

^c 1-{N-[(S)-1-Ethoxycarbonyl-3-cyclohexylpropyl]-l-alanyl}-l-proline.

^d (S)-Ethyl 2-[(3S,8aS)-3-methyl-1,4-dioxohexahydropyrrolo[1,2-α]pyrazin-2(1H)-yl]-4-phenylbutanoate.

5 SPECIFIC TESTS

Optical Rotation (781S), Procedures, Specific Rotation

Sample solution: 10 mg/mL in methanol

Acceptance criteria: −41.0° to −43.5°

Loss on Drying (731)

Analysis: Dry under vacuum at a pressure not exceeding 5 mm of mercury at 60° for 2 h.

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

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