Trandolapril

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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C₂₄H₃₄N₂O₅ 430.54

1H-Indole-2-carboxylic acid, octahydro N-[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]-1-alanyl (2S,3aR,7aS);

(2S,3aR,7aS)-1-[(S)-N-[(S)-1-Carboxy-3-phenylpropyl]alanyl]hexahydro-2-indolinecarboxylic acid, 1-ethyl ester CAS RN®: 87679-37-6.

1 DEFINITION

Trandolapril contains NLT 98.0% and NMT 102.0% of trandolapril (C₂₄H₃₄N₂O₅), calculated on the anhydrous basis.

2 IDENTIFICATION

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

Change to read:

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

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3.1 Procedure

Buffer: 6.8 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 3.0.

Mobile phase: Acetonitrile and Buffer (35:65)

Standard stock solution: 0.1 mg/mL of USP Trandolapril RS in Mobile phase

Standard solution: 0.002 mg/mL of USP Trandolapril RS in Mobile phase from Standard stock solution

Sample stock solution: 0.1 mg/mL of Trandolapril in Mobile phase

Sample solution: 0.002 mg/mL of Trandolapril in Mobile phase from Sample stock solution

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 210 nm
• Column: 4.6-mm × 15-cm; 3.5-µm packing L1
• Column temperature: 40°
• Flow rate: 1 mL/min
• Injection volume: 100 µL
• Run time: NLT 5.5 times the retention time of trandolapril

System suitability

• Sample: Standard solution
• Suitability requirements
• Tailing factor: NMT 2.0
• Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of trandolapril (C₂₄H₃₄N₂O₅) in the portion of Trandolapril taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of trandolapril from the Sample solution

rₛ = peak response of trandolapril from the Standard solution

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

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

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

4 IMPURITIES

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4.1 Residue on Ignition 〈281〉

Sample: 2.0 g

Acceptance criteria: NMT 0.1%

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4.2 Organic Impurities

Buffer: 6.8 g/L of monobasic potassium phosphate. Adjust with phosphoric acid to a pH of 2.5 ± 0.1.

Solution A: Acetonitrile and Buffer (25:75), filtered and degassed

Solution B: Acetonitrile and Buffer (50:50), filtered and degassed

Mobile phase: See Table 1.

Table 1

System suitability solution: 0.05 mg/mL each of USP Trandolapril Related Compound C RS and USP Trandolapril Related Compound D RS in Solution A

Standard solution: 0.0025 mg/mL of USP Trandolapril RS in Solution A

Sample solution: 2.5 mg/mL of Trandolapril in Solution A

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 210 nm
• Column: 4.6-mm × 15-cm; 3.5-µm packing L1
• Column temperature: 40°
• Flow rate: 1.3 mL/min
• Injection volume: 20 µL

System suitability

• Samples: System suitability solution and Standard solution
• Suitability requirements
• Resolution: NLT 4 between trandolapril related compound C and trandolapril related compound D, System suitability solution
• Tailing factor: NMT 1.5, Standard solution
• Relative standard deviation: NMT 3.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each specified or any unspecified impurity in the portion of Trandolapril taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × (1/F) × 100

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

rₛ = peak response of trandolapril from the Standard solution

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

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

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. [Note-Do not include trandolapril related compound D in the total impurities.]

Table 2

5 SPECIFIC TESTS

5.1 Optical Rotation, 〈781S〉 Procedures, Specific Rotation

Sample: 0.02 g/mL in dehydrated alcohol

Acceptance criteria: −16.5° to −18.5° at 20°

5.2 Water Determination, 〈921〉 Method I, Method Ic

Sample: 2 g

Acceptance criteria: NMT 0.2%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers. Store at room temperature.

USP Reference Standards 〈11〉

USP Trandolapril RS

USP Trandolapril Related Compound C RS

(2S,3aR,7aS)-1-[N-[(S)-1-Carboxy-3-cyclohexylpropyl]-l-alanyl]hexahydro-2-indolinecarboxylic acid 1-ethyl ester.

C₂₄H₄₀N₂O₅ 436.58

USP Trandolapril Related Compound D RS

(S)-Ethyl 2-[(3S,5aS,9aR,10aS)-3-methyl-1,4-dioxodecahydropyrazino[1,2-a]indol-2(1H)-yl)]-4-phenylbutanoate.

C₂₄H₃₂N₂O₄ 412.52