Enalapril Maleate and Hydrochlorothiazide 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 and Hydrochlorothiazide Tablets contain NLT 90,0% and NMT 110.0% of the labeled amounts of enalapril maleate (C₂₀H₂₈N₂O₅ · C₄H₄O₄) and hydrochlorothiazide (C₇H₈CIN₃O₄S₂).

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 for Enalapril Maleate.

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

3 ASSAY

ENALAPRIL MALEATE

Buffer: 136 mg/L of monobasic potassium phosphate in water. Initially add water to 80% of the total volume, adjust with phosphoric acid to a pH of 2.0, and dilute with water to volume. Adjust the pH before makeup to final volume.

Mobile phase: Acetonitrile and Buffer (400:600)

Standard solution: 0.2 mg/ml of USP Enalapril Maleate RS prepared as follows. Dissolve a suitable amount of USP Enalapril Maleate RS in about 25% of the total volume with methanol, and dilute to volume with Buffer.

Sample solution: Transfer a portion of the powder from NLT 20 Tablets, equivalent to 40 mg of enalapril maleate, to a 200-ml, volumetric flask. Add 50 ml. of Buffer, and sonicate for 15 min. Add 50 mL of methanol, sonicate for an additional 15 min, dilute with Buffer to volume. and filter.

Chromatographic system

(See Chromatography (621), System Suitability)

Mode: LC

Detector: UV 215 nm

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

Column temperature: 65°

Flow rate: 1.5 mL/min

Injection volume: 50 μL

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 700 theoretical plates

Tailing factor: NMT 3.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of enalapril maleate (C₂₀H₂₈N₂O₅ · C₄H₄O₄) in the portion of Tablets taken:

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

r_U = peak response of enalapril from the Sample solution

r_S = peak response of enalapril 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: 90.0%-110.0%

HYDROCHLOROTHIAZIDE

Buffer: Prepare as directed in the Assay for Enalapril Maleate

Mobile phase: Acetonitrile and Buffer (100:900)

Standard solution: 0.1 mg/mL of USP Hydrochlorothiazide RS prepared as follows. Dissolve a suitable quantity of USP Hydrochlorothiazide RS in 25% of the total volume of methanol, and dilute with Buffer to volume.

Sample solution: Transfer a portion of the powder from NLT 20 Tablets, equivalent to 20 mg of hydrochlorothiazide, to a 200-mL volumetric ask. Add 50 mL of Buffer, and sonicate for 15 min. Add 50 mL of methanol, sonicate for an additional 15 min, dilute with Buffer to volume, and filter.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 310 nm

Column: 4.6-mm × 20-cm; 10-μm packing L7

Column temperature: 30°

Flow rate: 2.5 mL/min

Injection volume: 50 μL

System suitability

Sample: Standard solution.

Suitability requirements

Column efficiency: NLT 1000 theoretical plates

Tailing factor: NMT 2:0

Capacity factor, KNLT 20

Relative standard deviation: NMT 2.0%

Analysis

Samples: Stenmand solution and Semple solution

Calculate the percentage of the labeled amount of bydrochlorothiaz (C₇H₈CIN₃O₄S₂) in the portion of Tablets taken

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

r_U = peak response of hydrochlorothiazide from the Sample solution

r_S = peak response of hydrochlorothiazide from the Standard solution

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

C_U = concentration of hydrochlorothiazide in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

Dissolution (711)

Enalapril maleate

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Standard solution: USP Elit Makuan RS Medum

Sample solution: Sample per Dizzaldion (711). Dilute with Afedium to a concemration similar to that of the Standant solution.

Analysis: Determine the percentage of the labeled amount of enalapni maleate (C₂₀H₂₈N₂O₅ · C₄H₄O₄) dissolved, using the test for Siniformity of Dosage Units, Procisture for content uniformity of enalapril males

Hydrochlorothiazide

Medium: Waterc 900 ml.

Apparatus 2: 50 rpm

Time: 30 min

Detector: UV 320 and 360 nm

Cell size: 1 cm

Standard solution: USP Hydrochlorothiazide RS dissolved in 20 mL of methanol and diluted with Medium

Sample solution: Sample per Dissolution (711). Dilute with Medium to a concentration that is similar to that of the Standard solution.:

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of hydrochlorothiazide (C₇H₈CIN₃O₄S₂) dissolved:

Result = (A_u/A_s) x (C_s/L) x V x D x 100

A_u = difference in absorbances (A₃₂₀ - A₃₆₀) at the wavelengths indicated for the Sample solution

A_s = difference in absorbarons (A₃₂₀ - A₃₆₀) at the wavelengths indicated for the Standard solution

C_s = concentration of hydrochlorothiazide in the Standard solution (mg/mL)

L = label claim of hydrochlorothiazide (mg/Tablet)

V = volume of Medium 900 mL

D = dilution factor of the Sample solution

Tolerances: NLT 80% (2) of the labelest amount of enalapril maleate (C₂₀H₂₈N₂O₅ · C₄H₄O₄)  and NLT 601% (0) of the labeled amount of Hydrochlorothiazide (C₇H₈CIN₃O₄S₂) are desolved.

Change to read:

Uniformity of Dosage Units (905): Meet the requirements

Procedure for content uniformity of enalapril maleate

Buffer: 136 g/L of monobasic potassium phosphate in water initially add water to 80% of the total volume, adjust with phosphoric acid to a pff of 4.0, and then dilute to volume with water

Solution A: Buffer and water (10:490)

Mobile phase: Acetonitrile water, and Buffer (150:340:10)

Standard solution: 100 g/ml. of Enalapril Maleate in Solution A

Sample solution: Transfer 1 finely powdered Tablet to a 50 ml volumetric flask, add 30 ml of Solution A, and sonicate for 15 min. Shake by mechanical means for 30 min, dilute with Solution A to volume, sonicate for 30 min, mix, and fitar, discarding the first portion of the Sitrate. Dilute a portion of the filtrate with Solution A to obtam a solution containing about 100 pg/ml

Chromatographic system

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm × 20-cm; 10-μm packing L7

Column temperature: 80°

Flow rate: 2 mL/min

Injection volume: 50 μL

System suitability

Sample: Standard solution

Suitability requirements

Column e

ciency: NLT 1000 theoretical plates

Tailing factor: NMT 2.0

Capacity factor, k′: NLT 2.5

Relative standard deviation: NMT 2.0%

Analysis

Capacity factor, k NLT 2.5

OFFICIAL

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of enalapril maleate (C₂₀H₂₈N₂O₅ · C₄H₄O₄) in the Tablet taken:

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

r_U = peak response of Enalapril Maleate from the Sample solution

r_S = peak response of Enalapril Maleate from the Standard solution

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

C_U = nominal concentration of Enalapril Maleate in the Sample solution (μg/mL)

Acceptance criteria: Moot the requirements

Procedure for content uniformity of hydrochlorothiazide

Buffer and Solution A: Prepare an directed in Procedure for conteme uniformity of enalapril massate

Standard stock solution: 0.25 mg/mL of USP Hydrochlorothiazide RS prepared as follows. Dissolve a suitable amount of USP Hydrochlorothiazide RS in 10% of the total volume of methanol, and dilute with Solution A to volume.

Standard solution: 50 µg/mL of Stochlottide RS in Solution A from Standard stock solution

Sample stock solution: Transfer 1 Tablet to a volumetric ask of a suitable size such that, when the hydrochlorothiazide is dissolved from the Tablet, a solution having a concentration of about 250 μg/mL is obtained. Add a volume of Solution A equal to about half the capacity of the ask, and sonicate with occasional shaking for 15 min. Shake by mechanical means for 30 min, dilute with Solution A to volume, and sonicate for 30 more min. Filter, and discard the first portion of the filtrate.

Sample solution: Transfer 50 mL of the clear fitrate to a 25 ml, volumetric flack, and dilute with Solution A to volume

Instrumental conditions

Mode: UV-Vis

Analytical wavelength: 320 and 360 nm

Cell: 1 cm

Blank: Solution A

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amounts of hydrochlorothiazide (C₇H₈CIN₃O₄S₂) in the Tablet taken:

Result = (A_u/A_s)x (C_s/L) x V x D x 100

A_u = difference in absorbances (A₃₂₀ - A₃₆₀) at the wavelengths indicated for the Sample solution

A_s = difference in absorbarons (A₃₂₀ - A₃₆₀) at the wavelengths indicated for the Standard solution

C_s = concentration of hydrochlorothiazide in the Standard solution (mg/mL)

L = label claim of hydrochlorothiazide (mg/Tablet)

V = volume of Medium 900 mL

D = dilution factor of the Sample solution

5 IMPURITIES

Buffer, Mobile phase, and Sample solution: Proceed as directed in the Assay for Enalapril Maleate.

Enalaprilst stock solution: 0.4 mg/ml of USP Enslumilat RS, in water

Enalapril diketopiperazine solution: Carefully place 20 mg of USP Enalabril Maleate 85 in 100-ml, besker to form a mound on the bottom of The besiker. Place the beaker on a hot plate at about one-half the maximum hot plate temperature setting Heat for about 5-10 min until the solid is melted. Immediately remove the beaker from the hot plate, and allow to cool. To the cooled residue in the beaker add 50 mL of acetonitrile, and conicate for a few min to dissolve. The solution typically contains between 0.2 and 0.4 mg/ml of enalapril iketopipeazine Nom Avoid overheating to prevent feat-induced degradation, which gives rise to a brown color

Standard solution: Transfer about 40 mg of USP Enalaudi Maleste RS, accurately weigheil to a 200-ml, volumetric flask, and dissolve with ahout 50 m. of methanol Pipet 1 mi each of Enalaprile stock solution and Enalapri diletopiperazine solution into the volumetric flask, ant dilute with Buffer to volume

Chromatographic system

(See Chromatography (621), System Suitability.)

Detector: UV 215mm

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

Column temperature: 65°

Flow rate: 1.5 mL/min

Injection volume: 50 μL

System suitability

Sample: Standard solution

[[Note-The relative retention times for enalaprilet, enalapri diketopiperazine, and enalapril are 0.3.0.4 and 1.0 respectively,]

Sultability requirements

Resolution: NLT 1.2 between enalapri and any peak

Column efficiency: NCT 700 theoretical plates for enalapril, NLT 1500 for enalaprilat, and NCT 1500 for enalapril diketopiperще

Talling factor: NMT 3.5

Rulative standard deviation: NMT 5.0%, for enalaprilat and inalapril ditopperazine, and NMT 2.0% for enalapril

Analysis

Samples: Standard solution and Sample solution

Calafate the perzsentage of enalaprilat in the portion of Tablets taken

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

r_U = peak response of Enalapril Maleate from the Sample solution

r_S = peak response of Enalapril Maleate 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)

Calimate the percentage of enalapril diketopiprazne in the portion of Tablets taken:

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

r_U = peak response of Enalapril diketopiperazine from the Sample solution

r_S = peak response of Enalapril diketopiperazine from the Standard solution

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

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

Acceptance criteria: NMT 5.0% of total impurities

ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers.