Ramipril 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 

Ramipril Tablets contain NLT 90.0% and NMT 105.0% of the labeled amount of ramipril (C₂₃H₃₂N₂O₅). 

2 IDENTIFICATION 

Change to read: 

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

Sample: Finely powder a suitable number of Tablets and transfer a portion of the powder, equivalent to 100 mg of ramipril, to a suitable beaker. Add 25 mL of methanol, shake to dissolve, and pass through the filter. Evaporate the solution in air and heat to complete dryness at 105° for 1 h. 

Acceptance criteria: Meet the requirements 

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. 

ASSAY Procedure 

Solution A: 2 g of sodium perchlorate in a mixture of 0.5 mL of triethylamine and 800 mL of water. Adjust with phosphoric acid to a pH of 3.6, and add 200 mL of acetonitrile. 

Solution B: 2 g of sodium perchlorate in a mixture of 0.5 mL of triethylamine and 300 mL of water. Adjust with phosphoric acid to a pH of 2.6, and add 700 mL of acetonitrile. 

Mobile phase: Solution A and Solution B (60:40) 

Diluent: 6.8 g of monobasic sodium phosphate in 500 mL of water. Add 1000 mL each of methanol and acetonitrile. Adjust with phosphoric acid to a pH of 5.5. 

Standard solution: 0.1 mg/mL of USP Ramipril RS in Diluent 

Sample stock solution: Nominally 0.25 mg/mL of ramipril from NLT 10 Tablets prepared as follows. Add 50% of the nal volume of Diluent to the flask and sonicate to disperse the Tablets. Sonicate for an additional 30 min and dilute with Diluent to volume. Sample solution: Nominally 0.1 mg/mL of ramipril from the Sample stock solution in Diluent. 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 L1 

Column temperature: 50° 

Flow rate: 1 mL/min 

Injection volume: 10 µL 

Run time: 15 min 

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 ramipril (C₂₃H₃₂N₂O₅) in the portion of Tablets taken: 

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response of ramipril from the Sample solution 

r_S = peak response of ramipril from the Standard solution 

C_S = concentration of ramipril in the Sample solution (mg/mL)

C_U = nominal concentration of ramipril in the Standard solution (mg/mL) 

Acceptance criteria: 90.0%–105.0% 

3 PERFORMANCE TESTS 

Dissolution 〈711〉 

Medium: 0.1 N hydrochloric acid; 500 mL 

Apparatus 2: 50 rpm 

Time: 30 min 

Standard stock solution: 0.25 mg/mL of USP Ramipril RS in methanol 

Standard solution: (L/500) mg/mL of USP Ramipril RS in Medium from the Standard stock solution where L is the label claim of ramipril in mg/Tablet 

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

Solution A, Solution B, Mobile phase, Chromatographic system, and System suitability: Proceed as directed in the Assay except for the Injection volume. 

Injection volume: 100 µL 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of ramipril (C₂₃H₃₂N₂O₅) dissolved: 

Result = (r_U/r_S) × C_S × V x (1/L) x 100  

r_U = peak response from the Sample solution 

r_S = peak response from the Standard solution 

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

V = volume of Medium, 500 mL

L = label claim for ramipril (mg/Tablet) 

Tolerances: NLT 80% (Q) of the labeled amount of ramipril (C₂₃H₃₂N₂O₅) is dissolved. 

Uniformity of Dosage Units 〈905〉: Meet the requirements 

4 IMPURITIES 

Organic Impurities 

Solution A and Solution B: Prepare as directed in the Assay. 

Mobile phase: See Table 1. 

Table 1 

System suitability solution: 50 µg/mL each of USP Ramipril RS, USP Ramipril Related Compound A RS, and USP Ramipril Related Compound D RS in Solution B 

Sensitivity solution: 1 µg/mL of USP Ramipril RS in Solution B 

Standard solution: 0.005 mg/mL of USP Ramipril RS in Solution B 

Sample solution: Nominally 1 mg/mL of ramipril prepared as follows. Finely powder NLT 20 Tablets and transfer a portion of the powder to an appropriate volumetric flask. Add about 60% of the flask volume of Solution A, and sonicate for 30 min with intermittent shaking to dissolve. Dilute with Solution A to volume. Pass a portion of the solution through a suitable filter of 0.45-µm pore size. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 210 nm 

Column: 4.0-mm × 25-cm; 3-µm packing L1 

Column temperature: 65° 

Flow rate: 1 mL/min 

Injection volume: 10 µL 

System suitability 

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

Suitability requirements 

Resolution: NLT 3.0 between ramipril related compound A and ramipril, System suitability solution 

Relative standard deviation: NMT 5.0%, Standard solution 

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

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of each degradation product in the portion of Tablets taken: 

Result = (r_U/r_S) × (C_S/C_U) × 100 × (1/F) 

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

r_S = peak response of ramipril from the Standard solution 

C_S = nominal concentration of ramipril in the Sample solution (mg/mL)

C_U = concentration of USP Ramipril RS in the Standard solution (mg/mL) 

F = relative response factor (see Table 2) 

Acceptance criteria: See Table 2. Disregard any peak less than 0.04%. 

Table 2 

^aThis is a process impurity monitored in the drug substance that is for identification only. It is not included in the total degradation products. 

^b(2S,3aS,6aS)-1-[(S)2-[[(S)-1-(Methylethoxy)carbonyl-3-phenylpropyl]amino]-1-oxopropyl]-octahydrocyclopenta[b]pyrrole-2-carboxylic acid. c Ethyl (2S)2-[(3S,5aS,8aS,9aS)-3-methyl-1,4-dioxodecahydro-1H-cyclopenta[e]pyrrolo[1,2-a]pyrazin-2-yl]-4-phenyl-butanoate. d Not included in the total degradation products. 

5 ADDITIONAL REQUIREMENTS 

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

USP Reference Standards 〈11〉 

USP Ramipril RS 

USP Ramipril Related Compound A RS 

(2S,3aS,6aS)-1-[(S)2-[[(S)-1-(Methoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-octahydrocyclopenta[b]pyrrole-2-carboxylic acid.C₂₂H₃₀N₂O₅402.48 

USP Ramipril Related Compound D RS 

Ethyl (2S)2-[(3S,5aS,8aS,9aS)-3-methyl-1,4-dioxodecahydro-1H-cyclopenta[e]pyrrolo[1,2-a]pyrazin-2-yl]-4-phenyl-butanoate. C₂₂H₃₀N₂O₄ 398.50