Perindopril Erbumine 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

Perindopril Erbumine Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of perindopril erbumine (C₁₉H₃₂N₂O₅·C₄H₁₁N).

2 IDENTIFICATION

A. The UV absorption spectra of the major peak of the Sample solution exhibit maxima and minima at the same wavelengths as those of the corresponding peak of the Standard solution, as obtained in the Assay.

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

3.1 PROCEDURE

Solution A: Dissolve 0.92 g of sodium 1-heptanesulfonate in 1 L of water and add 1 mL of triethylamine. Adjust with a solution of perchloric acid and water (1:1) to a pH of 2.0.

Mobile phase: Acetonitrile and Solution A (38:62)

Diluent: Acetonitrile and Solution A (40:60)

Standard solution: 0.08 mg/mL of USP Perindopril Erbumine RS in Diluent prepared as follows. Dissolve a suitable quantity of USP Perindopril Erbumine RS in 80% of the total volume of Diluent, sonicate for 5 min, and dilute with Diluent to volume. Pass through a suitable filter of 0.45-µm pore size and discard the first 3 mL of filtrate.

Sample solution: Nominally equivalent to 0.08 mg/mL of perindopril erbumine in Diluent prepared as follows. Weigh and transfer the number of Tablets into a suitable volumetric flask, as indicated in Table 1.

Table 1

Add Diluent to about 70% of the flask volume, shake mechanically for about 60 min at 180 rpm, and sonicate for 20 min. Dilute with Diluent to volume. Pass through a suitable filter of 0.45-µm pore size and discard the first 3 mL of filtrate.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4-mm × 25-cm; 4-µm packing L7

Temperatures

Column: 60°

Sample cooler: 5°

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 2.5 times the retention time of perindopril

3.3 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of perindopril erbumine (C₁₉H₃₂N₂O₅·C₄H₁₁N) in the portion of Tablets taken:

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

C_U = nominal concentration of perindopril erbumine in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Solution A: Proceed as directed in the Assay.

Mobile phase: Acetonitrile and Solution A (350:650)

Standard stock solution: 0.55 mg/mL of USP Perindopril Erbumine RS in acetonitrile

Standard solution: Prepare solutions of USP Perindopril Erbumine RS in Medium from the Standard stock solution, with final concentrations from Table 2.

Table 2

Sample solution: Pass a portion of the solution under test through a suitable filter and discard the first 1 mL of filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm x 15-cm; 5-µm packing L7

Column temperature: 50°

Flow rate: 1.2 mL/min

Injection volume: 100 µL

Run time: NLT 1.6 times the retention time of perindopril

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of perindopril erbumine (C₁₉H₃₂N₂O₅·C₄H₁₁N) dissolved.

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

Tolerances: NLT 85% (Q) of the labeled amount of perindopril erbumine (C₁₉H₃₂N₂O₅·C₄H₁₁N) is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

ORGANIC IMPURITIES

Solution A: Proceed as directed in the Assay.

Solution B: Acetonitrile

Mobile phase: See Table 3.

Table 3

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

System suitability stock solution A: 0.03 mg/mL of USP Imidazole RS in Diluent

System suitability stock solution B: 0.12 mg/mL each of USP Perindopril Related Compound C RS and USP Perindopril Related Compound D RS in Diluent. Initially add 80% of the total volume of Diluent, sonicate for 5 min, and dilute with Diluent to volume.

System suitability solution: Accurately weigh about 1.5 mg each of USP Perindopril Related Compound B RS and USP Perindopril Related Compound F RS into a 50-mL volumetric flask. Add 30 mL of Diluent and sonicate for 5 min. Transfer 5.0 mL each of System suitability stock solution A, System suitability stock solution B, and Standard stock solution. Dilute with Diluent to volume.

Standard stock solution: 0.05 mg/mL of USP Perindopril Erbumine RS in Diluent prepared as follows. Dissolve a suitable quantity of USP Perindopril Erbumine RS in 80% of the total volume of Diluent, sonicate for 5 min, and dilute with Diluent to volume.

Standard solution: 0.005 mg/mL of USP Perindopril Erbumine RS in Diluent from the Standard stock solution. Pass through a suitable filter of 0.45-µm pore size and discard the first 3 mL of filtrate.

Sample solution: Nominally equivalent to 2 mg/mL of perindopril erbumine in Diluent prepared as follows. Transfer a quantity equivalent to about 20 mg of perindopril erbumine from powdered Tablets (NLT 20) into a test tube. Pipet 10.0 mL of Diluent into the test tube, sonicate for about 10 min, and vortex for about 1 min. Pass through a suitable filter of 0.45-µm pore size and discard the first 3 mL of filtrate.

(See Chromatography (621), System Suitability.)

Chromatographic system

Proceed as directed in the Assay, except for the Run time. [NOTE-The run time is determined by the gradient from Table 3.]

System suitability

Sample: System suitability solution

Suitability requirements

Tailing factor: NMT 1.5 for the perindopril peak

Relative standard deviation: NMT 5.0% for the perindopril peak

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Tablets taken:

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of perindopril erbumine from the Standard solution

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

C_U = nominal concentration of perindopril erbumine in the Sample solution (mg/mL)

F = relative response factor for each individual impurity (see Table 4)

Acceptance criteria: See Table 4. Disregard peaks less than 0.1%.

Table 4

^a Imidazole is given for identification only and is not quantitated using this procedure.

^b (2S,3aS,7aS)-1-((S)-2-[(S)-1-Carboxybutylamino]propanoyl}octahydro-1H-indole-2-carboxylic acid.

^c (S)-2-{(3S,5aS,9aS,10aS)-3-Methyl-1,4-dioxodecahydropyrazino[1,2-a]indol-2(1H)-yl}pentanoic acid.

^d (S)-2-{(3S,5aS,9aS,10aR)-3-Methyl-1,4-dioxodecahydropyrazino[1,2-a]indol-2(1H)-yl}pentanoic acid.

^e (S)-Ethyl 2-{(3S,5aS, 9aS,10aS)-3-methyl-1,4-dioxodecahydropyrazino[1,2-a]indol-2(1H)-yl}pentanoate.

^f Total impurities excludes perindopril related compound F and perindopril related compound B.

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in air-tight containers. Protect from heat and moisture.

6.2 USP REFERENCE STANDARDS (11)

USP Imidazole RS

USP Perindopril Erbumine RS

USP Perindopril Related Compound B RS

(2S,3aS,7aS)-1-{(S)-2-[(S)-1-Carboxybutylamino]propanoyl}octahydro-1H-indole-2-carboxylic acid.

C₁₇H₂₈N₂O₅ 340.41

USP Perindopril Related Compound C RS

(S)-2-{(3S,5aS,9aS,10aS)-3-Methyl-1,4-dioxodecahydropyrazino[1,2-a]indol-2(1H)-yl}pentanoic acid.

C₁₇H₂₆N₂O₄ 322.40

USP Perindopril Related Compound D RS

(S)-2-{(3S,5aS,9aS,10aR)-3-Methyl-1,4-dioxodecahydropyrazino[1,2-a]indol-2(1H)-yl}pentanoic acid.

C₁₇H₂₆N₂O₄ 322.40

USP Perindopril Related Compound F RS

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

C₁₉H₃₀N₂O₄ 350.45