Fosinopril Sodium 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

Fosinopril Sodium Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of fosinopril sodium (C₃₀H₄₅NNaO₇P).

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197F (CN 1-May-2020)

Sample: Transfer a portion of finely powdered Tablets, equivalent to 25 mg of fosinopril sodium, to a 100-mL beaker containing 40 mL of water. Heat at 25° for 5 min with stirring, and pass through a fritted-disc funnel of medium pore size. Centrifuge the filtrate at 2500 rpm for 30 min. Adjust the filtrate with phosphoric acid to a pH of 3 to precipitate the fosinopril, and pass through a fritted-disc funnel. Dissolve the precipitate by passing chloroform through the filter, and evaporate the chloroform solution to dryness under a current of air. Proceed as directed, using the oily residue so obtained.

Standard: Transfer 25 mg of USP Fosinopril Sodium RS to a 100-mL beaker containing 40 mL of water. Proceed as directed for the Sample, beginning with “Heat at 25° for 5 min with stirring”. Use the residue.

Acceptance criteria: Meet the requirements

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

Mobile phase: Methanol and 0.2% phosphoric acid (780:220)

Diluent: Acetonitrile and 0.2 M Urea solution (20:80)

System suitability solution: 30 μg/mL of USP Fosinopril Related Compound A RS and 70 μg/mL of USP Fosinopril Sodium RS in Diluent

Standard solution: 0.1 mg/mL of USP Fosinopril Sodium RS in Diluent

Sample stock solution: Transfer NLT 10 Tablets to a 500-mL volumetric flask, add 400 mL of Diluent, and stir for 40 min. Dilute with Diluent to volume, mix, and centrifuge. Use the clear supernatant.

Sample solution: Nominally 0.1 mg/mL of fosinopril sodium in Diluent from Sample stock solution

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.0-mm × 30-cm; packing L1

Flow rate: 2 mL/min

Injection volume: 50 μL

Run time: NLT 1.5 times the retention time of the fosinopril peak

3.3 System suitability

Samples: System suitability solution and Standard solution

[Note - The relative retention times for fosinopril related compound A and fosinopril are about 0.4 and 1.0, respectively.]

3.4 Suitability requirements

Resolution: NLT 2.0 between the fosinopril and fosinopril related compound A peaks, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fosinopril sodium (C₃₀H₄₅NNaO₇P) in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of fosinopril from the Sample solution

r_S = peak response of fosinopril from the Standard solution

C_S = concentration of USP Fosinopril Sodium RS in the Standard solution (mg/mL)

C_U = nominal concentration of fosinopril sodium in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Mobile phase: Acetonitrile and 0.2% phosphoric acid (640:360)

System suitability solution: 0.02 mg/mL each of USP Fosinopril Sodium RS and USP Fosinopril Related Compound G RS in Mobile phase

Standard stock solution: 0.1 mg/ml of USP Fosinopril Sodium RS prepared as follows. Add methanol, about 3% of the total volume, to a suitable quantity of USP Fosinopril Sodium RS in a suitable volumetric flask, sonicate briefly, and dilute with Medium to volume.

Standard solution: Dilute the Standard stock solution with Medium as directed in Table 1.

Table 1

Sample solution: Pass portions of the solution under test through a 1.2-μm Acrylic filter. [Note - Do not use glass filters.]

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm × 15-cm; 5-μm packing L1

Column temperature: 40°

Flow rate: 3 mL/min

Injection volume: 50 μL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.7 between fosinopril and fosinopril related compound G, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fosinopril sodium (C₃₀H₄₅NNaO₇P) dissolved.

Tolerances: NLT 80% (Q) of the labeled amount of fosinopril sodium (C₃₀H₄₅NNaO₇P) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Limit of Fosinopril Related Compound A

Mobile phase, Diluent, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Standard stock solution: 0.1 mg/mL of USP Fosinopril Related Compound A RS in methanol

Standard solution: 0.0025 mg/mL of USP Fosinopril Related Compound A RS in Diluent from Standard stock solution

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of fosinopril related compound A in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of fosinopril related compound A from the Sample solution

r_S = peak response of fosinopril related compound A from the Standard solution

C_S = concentration of fosinopril related compound A in the Standard solution (mg/mL)

C_U = nominal concentration of fosinopril sodium in the Sample solution (mg/mL)

Acceptance criteria: NMT 4%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP Fosinopril Related Compound A RS

(4S)-4-Cyclohexyl-[(4-phenylbutyl)phosphinyl]acetyl-l-proline.

C₂₃H₃₄NO₅P 435.49

USP Fosinopril Related Compound G RS

(4-Phenylbutyl)phosphinylacetic acid, disodium salt.

C₁₂H₁₅Na₂O₄ P 300.20

USP Fosinopril Sodium RS