Trandolapril 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

Trandolapril Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of trandolapril (C₂₄H₃₄N₂O₅).

2 IDENTIFICATION

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

B. The UV spectrum 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: To 1 L of 8.9 g/L of dibasic sodium phosphate anhydrous, add 1 mL of triethylamine and adjust with phosphoric acid to a pH of 3.5. Pass through a suitable fllter of 0.45-µm pore size.

Mobile phase: Acetonitrile and Buffer (40:60)

Diluent: Acetonitrile and water (40:60)

Standard solution: 40 µg/mL of USP Trandolapril RS in Diluent prepared as follows. Transfer a suitable quantity of USP Trandolapril RS to a suitable volumetric flask. Add Diluent up to 70% of the flask volume. Sonicate if necessary. Dilute with Diluent to volume.

Sample solution: Nominally 40 µg/mL of trandolapril in Diluent prepared as follows. Transfer a suitable quantity of trandolapril from NLT 10 Tablets to a suitable volumetric flask. Add Diluent up to 70% of the flask volume. Sonicate up to 30 min, if necessary, with occasional swirling. Dilute with Diluent to volume. Pass a portion of the solution through a membrane fllter of 0.45-µm pore size.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 216 nm. For Identiflcation B, use a diode array detector in the range of 190–400 nm.
• Column: 4.6-mm × 15-cm; 3-µm packing L1
• Flow rate: 1.2 mL/min
• Injection volume: 20 µL
• Run time: NLT 2 times the retention time of trandolapril

System suitability

• Sample: Standard solution
• Suitability requirements
• Column eflciency: NLT 3000 theoretical plates
• 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 trandolapril (C₂₄H₃₄N₂O₅) in the portion of Tablets 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 (µg/mL)

Cᵤ = nominal concentration of trandolapril in the Sample solution (µg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

4.1 Dissolution 〈711〉

Medium: Water, deaerated; 500 mL

Apparatus 2: 50 rpm

Time: 45 min

Mobile phase and System suitability: Proceed as directed in the Assay.

Standard stock solution: 0.2 mg/mL of USP Trandolapril RS prepared as follows. Transfer a suitable quantity of USP Trandolapril RS to a suitable volumetric flask. Add acetonitrile to about 5% of the flask volume, sonicate to dissolve, and dilute with Medium to volume.

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

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

Chromatographic system: 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 trandolapril (C₂₄H₃₄N₂O₅) dissolved:

Result = (rᵤ/rₛ) × (Cₛ/L) × V × 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)

L = label claim (mg/Tablet)

V = volume of Medium, 500 mL

Tolerances: NLT 80% (Q) of the labeled amount of trandolapril (C₂₄H₃₄N₂O₅) is dissolved.

4.2 Uniformity of Dosage Units 〈905〉

Meet the requirements

5 IMPURITIES

5.1 Organic Impurities

Buffer: To 1 L of 7.0 g/L of sodium perchlorate monohydrate in water (0.05 M), add 2 g of octanesulfonic acid sodium salt followed by 1 mL of triethylamine. Adjust with diluted perchloric acid (1 in 10) to a pH of 2.0. Pass through a membrane fllter of 0.45-µm pore size.

Solution A: Acetonitrile, tetrahydrofuran, and Buffer (11:1:28)

Solution B: Acetonitrile and Buffer (75:25)

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and Buffer (40:60)

Standard stock solution 1: 0.06 mg/mL each of USP Trandolapril Related Compound C RS and USP Trandolapril Related Compound D RS in acetonitrile. Sonicate to dissolve.

System suitability solution: 0.6 mg/mL of USP Trandolapril RS and 6 µg/mL each of USP Trandolapril Related Compound C RS and USP Trandolapril Related Compound D RS from Standard stock solution 1 in Diluent. Add Diluent up to 70% of the flask volume, sonicate to dissolve, and cool to room temperature. Dilute with Diluent to volume.

Standard stock solution 2: 0.3 mg/mL of USP Trandolapril RS in Diluent prepared as follows. Transfer a suitable quantity of USP Trandolapril RS to a suitable volumetric flask. Add Diluent up to 70% of the flask volume, sonicate, and cool to room temperature. Dilute with Diluent to volume.

Standard solution: 6 µg/mL of USP Trandolapril RS in Diluent from Standard stock solution 2.

Sample solution: Nominally 600 µg/mL of trandolapril in Diluent prepared as follows. Transfer a suitable quantity of trandolapril from NLT 15 Tablets to a suitable volumetric flask. Add Diluent up to 50% of the flask volume and sonicate for 30 min. Dilute with Diluent to volume.

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: 40°
• Flow rate: 1.5 mL/min
• Injection volume: 50 µL

System suitability

• Samples: System suitability solution and Standard solution
• Suitability requirements
• Resolution: NLT 3.0 between trandolapril related compound C and trandolapril related compound D, System suitability solution
• Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

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

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

rᵤ = peak response of each specifled and unspecifled degradation product from the Sample solution

rₛ = peak response of trandolapril from the Standard solution

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

Cᵤ = nominal concentration of trandolapril in the Sample solution (µg/mL)

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. Reporting threshold: 0.1%.

Table 2

^a (2S,3aR,7aS)-1-[N-[(S)-1-Carboxy-3-phenylpropyl]-l-alanyl]hexahydro-2-indolinecarboxylic acid.

^b Process-related impurity used for resolution measurement only.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at controlled 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 hydrochloride.

C₂₄H₄₀N₂O₅ · HCl 473.05

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