Enalapril Maleate 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

Enalapril Maleate Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of enalapril maleate (C₂₀H₂₈N₂O₅ · C₄H₄O₄).

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.

3 ASSAY

PROCEDURE

Buffer: Dissolve 1.38 g of monobasic sodium phosphate in 800 mi, of water, adjust with phosphoric acid to a pH of 2.2, and dilute with water to 1000 ml.

Mobile phase: Acetonitrile and Buffer (250:750)

Enalapril diketopiperazine solution: Place 20 mg of USP Enalapril Maleate RS in a 100-mL beaker to form a mound on the bottom of the beaker. Place the beaker on a hot plate at one half the maximum hot plate temperature setting to melt the solid. When melting is observed (after 5-10 min of heating), immediately remove the beaker from the hot plate, and allow it to cool. Avoid overheating beyond the melting initially observed to prevent heat-induced degradation, which would give rise to a brown color.

To the cooled residue in the beaker add 50 ml. of acetonitrile, and sonicate for a few min to dissolve the residue. The solution typically contains between 0.2 and 0.4 mg/ml of enalapril diketopiperazine

Enalaprilat stock solution: 0.4 mg/mL of USP Enalaprilat RS in water

Standard solution: 0.2 mg/ml of USP Enalapril Maleate RS and 0.002 mg/mL of USP Enalaonilat RS in Buffer prepared as follows. To a suitable amount of USP Enalapril Maleate RS in a suitable volumetric flask add an appropriate amount of Enalaprilat stock solution to the flask, and add 50% of the total volume of Buffer to dissolve. Sonicate if necessary, then dilute with Buffer to volume.

System suitability solution: Dilute 0.5 ml of Enalapril diketopiperazine solution with Standard solution to a final volume of 25 mL

Sample solution: Nominally 0.2 mg/ml. of enalapril maleate in Buffer prepared as follows. Transfer NLT 10 Tablets to a volumetric flask of capacity such that when filled to volume it will produce a 0.2-mg/mL solution. Add a volume of Buffer that is about one-half the nominal volume of the flask, sonicate for 15 min, and shake by mechanical means for 30 min. Dilute with Buffer to volume, shake well, and sonicate for another 15 min. Pass the solution through a suitable filter of of 0.45-um pore size, and discard the first portion of the filtrate.

Chromatographic system

(See Chromatography (621) System Suitability)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm x 25-cm; 5-um packing L7

Column temperature: 50°

Flow rate: 2 mL/min

Injection volume: 50 µL

System suitability

Samples: Standard solution and System suitability solution

[Nort-The relative retention times for maleic acid, enalaprilat, enalapril, and enalapril diketopiperazine are about 0.3, 0.5, 1.0, and 1.5, respectively, System suitability solution. A peak response for a heat-induced degradation product of enalapril diketopiperazine (if present

with a relative retention time of about 1.2) is NMT 15% of the response for enalapril diketopiperazine.]

Suitability requirements

Resolution: NLT 2.0 between maleic acid and enalaprilat; NLT 2.0 between enalaprilat and enalapril; NLT 2.0 between enalapril and

enalapril diketopiperazine, System suitability solution

Column efficiency: NLT 1000 theoretical plates for enalaprilat; NLT 300 theoretical plates for enalapril, NLT 2500 theoretical plates for enalapril diketopiperazine, System suitability solution

Tailing factor: NMT 2.0 for enalapril, System suitability solution

Relative standard deviation

Enalapril peak: NMT 2.0%, Standard solution

Enalaprilat peak: Responses agree within 5%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amoum of enslapni maleste (CHNO, CHO) in the portion of Tablets taken:

Result = (r_U/(r_S) × (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 Enalapril Maleate RS in the Standard solution (mg/ml)

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

Acceptance criteria: 910.00-110.0%

4 PERFORMANCE TESTS

Dissolution (711)

Medium: pH 6.8 phosphate buffer (see Reagents, Indicators, and Solutions—Buffer Solutions); 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Standard solution: 0.1 mg/mL of USP Enalapril Maleate RS in Medium. Sonicate if necessary. Dilute in Medium per Table 1.

Sample solution: Paas a portion of solution under test through a suitable iter Dilute as needed with Medium to a moncentration that in similar to that of the Standard sciution

Analysis: Determine the amount of Enalapril Maleate (C₂₀H₂₈N₂O₅ · C₄H₄O₄) dissolved as directed in informity of Dusage tits 1908

Tolerances: NLT 80% (0) of the labeled amount of Enalapril Maleate (C₂₀H₂₈N₂O₅ · C₄H₄O₄) is dissolved.

Change to read

Uniformity of Dosage Units: Meet the requirements

Procedure for content uniformity

Buffer and Mobile phase: Prepare as directed in the Assay

Standard solution: 00.1 mg/mL of USP Enalapril Maleate RS in Buffer

Sample solution: 0.3 mgime of enalapril maleate from 1 Tablet in Buffer. Add a volume of Buffer that is one half the nominal volume of the flask, sonicate for 15 min and shake by mechanical means for 30 min. Dilute with Buffer to anlume, shake well, ant sonicate for an additional 15 min. Pass through a suitable filter of 0.45-um pore size, and discard the first portion of the fitbrate

Chromatographic system

Modie: LC

Detector: UV 215 nm

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

Column temperature: 50°

Flow rate: 2 mL/min

Injection volume: 50

System suitabidity

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 300 theoretical plates

Tailling factor: SMT 20

Capacity factor, NLT 1.5

Relative standard deviation NMT 2.0%

N-The enalaprit peak tailing factor may be minimized by combolling the column temperatum between 45 and 50 and by raising the pH of the aqueous component of the Mobile phase from 2.2 to 26 The capacity factor may be increased by decreasing the amount of acetonitrile in the Mobile phase

Analysis

Samples: Stardardottion and Sample solution

Calculate the percentage of the labelest amount of enalapri maleate (C₂₀H₂₈N₂O₅ · C₄H₄O₄) in the Tablet taken:

Result = (r_U/(r_S) × (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 Enalapril Maleate RS in the Standard solution (mg/ml)

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

5 IMPURITIES

Buffer, Mobile phase, Enalapril diketopiperazine solution, Standard solution, System suitability solution, Sample solution,

Chromatographic system, and System suitability: Proceed as directed in the Assay.

Diluted standand solution: Dilute 1.0 ml, of Standard solution with Buff to 100 ml

Analysis

Samples: Buffer, Standard solution, Sample solution, and Diluted standard sciuttan

Measure the responses for all of the peaks in the Sample sciution greater than 0:1 of the response of the enalapril peak that are not observed in the Bulle

Calculate the percentage of anhydrous enalaprilat (as enalapril maleate) in the portion of Tablets taken:

Result = (r_U/(r_S) × (C_S /C_U) x (M_r1/M_r2) x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

M = molecular weight of enalapril maleate, 492.52

M = molecular weight of anhydrous enalaprilat, 348.29

Calculate the percentage of enalapril diketopiperazine (as enalapril maleate) at the portion of Tableta takan

Result = (r_U/(r_S) × (C_S /C_U) x (1/F) x (M_r1/M_r2) x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

F = relative response factor of enalapril diketopiperazine, 1.25

M = molecular weight of enalapril maleate, 492.52

M = molecular weight of anhydrous enalaprilat, 348.29

Calculate the percentage of the sum of all other individual impurtties in the portion of Tablets taken:

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

r_U = sum of the responses of all other individual impunties other than maleic acid, enalapril, enalaprilat, and enalapril diketopiperazine from the Sample solution

r_S = peak response of enalapril maleate from the Diluted standard solution

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

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

Acceptance criteria: NMT 5.0% for the sum of all ampurities including those from enalapritat and enalapril datopiperazine

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers.