Fosinopril Sodium Tablets
» Fosinopril Sodium Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of fosinopril sodium (C30H45NNaO7P).
Packaging and storage— Preserve in tight containers, and store at controlled room temperature.
USP Reference standards 11
USP Fosinopril Sodium RS Click to View Structure
USP Fosinopril Related Compound A RS Click to View Structure
(4S)-4-Cyclohexyl-[(4-phenylbutyl)phosphinyl]acetyl-l-proline.
    C23H34NO5P     435.49
USP Fosinopril Related Compound G RS Click to View Structure
(4-Phenylbutyl)phosphinylacetic acid, disodium salt.
    C12H15Na2O4P     300.20
Identification—
A: Infrared Absorption 197F
Test specimen— Transfer a portion of the finely powdered Tablets, equivalent to about 25 mg of fosinopril sodium, to a 100-mL beaker containing 40 mL of water. Heat at 25 for 5 minutes with stirring, and pass through a medium-porosity fritted-disc funnel. Centrifuge the filtrate at 2500 rpm for 30 minutes. 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 and a similarly prepared residue from 25 mg of USP Fosinopril Sodium RS.
B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that of the Standard preparation, as obtained in the Assay.
Dissolution 711
Medium: water; 900 mL.
Apparatus 2: 50 rpm.
Time: 30 minutes.
Mobile phase— Prepare a filtered and degassed mixture of acetonitrile and 0.2% phosphoric acid (64:36). Make adjustments if necessary (see System Suitability under Chromatography 621).
Resolution solution— Prepare a solution in Mobile phase containing about 0.02 mg per mL each of USP Fosinopril Sodium RS and USP Fosinopril Related Compound G RS.
Standard stock solution— Accurately weigh about 20 mg of USP Fosinopril Sodium RS into a 200-mL volumetric flask, dissolve in 6-mL of methanol, sonicate briefly, and dilute with Medium to volume.
Standard solution— Dilute the Standard stock solution with Medium as directed in the following table.
Label claim Standard stock
solution (mL)
Final volume
(Flask size)
5 mg 5.0 100
10 mg 10 100
20 mg 20 100
40 mg 40 100
Test solution— Use portions of the solution under test passed through a 1.2-µm acrylic filter. [note—Do not use glass filters. ]
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 215-nm detector and a 4.6-mm × 15-cm column, maintained at a temperature of 40, that contains 5-µm packing L1. The flow rate is about 3 mL per minute. Chromatograph the Resolution solution and the Standard solution, and record the peak responses as directed for Procedure: the resolution, R, between fosinopril sodium and fosinopril related compound G is not less than 1.7; and the relative standard deviation for replicate injections of the Standard solution is not more than 2.0%.
Procedure— Separately inject equal volumes (about 50 µL) of the Test solution and the Standard solution having a known concentration of USP Fosinopril Sodium RS in the same Medium, and record the chromatograms. Measure the responses for the major peaks, and calculate the amount of C30H45NNaO7P dissolved.
Tolerances— Not less than 80% (Q) of the labeled amount of C30H45NNaO7P is dissolved in 30 minutes.
Uniformity of dosage units: meet the requirements.
Limit of related compound A—
Mobile phase, Diluent, and Chromatographic system— Proceed as directed in the Assay.
Standard solution— Dissolve an accurately weighed quantity of USP Fosinopril Related Compound A RS in methanol to obtain a solution having a known concentration of about 0.1 mg per mL. Dilute with Diluent to obtain a solution having a final known concentration of 0.0025 mg per mL.
Test solution— Use the Assay preparation.
Procedure— Separately inject equal volumes (about 50 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses for the major peaks. Calculate the percentage of fosinopril related compound A in the portion of Tablets taken by the formula:
1000C(rU / rS)
in which C is the concentration, in mg per mL, of the fosinopril related compound A in the Standard solution; and rU and rS are the peak responses obtained from the Test solution and the Standard solution, respectively. Not more than 4% is found.
Assay—
Mobile phase— Prepare a degassed mixture of methanol and 0.2% phosphoric acid (78:22). Make adjustments if necessary (see System Suitability under Chromatography 621).
Diluent— Prepare a mixture of 0.2 M urea solution and acetonitrile (80:20).
Resolution solution— Prepare a solution in Diluent containing 30 µg of USP Fosinopril Related Compound A RS and 70 µg of USP Fosinopril Sodium RS per mL.
Standard preparation— Dissolve an accurately weighed quantity of USP Fosinopril Sodium RS to obtain a solution having a known concentration of about 0.1 mg per mL.
Assay preparation— Transfer not fewer than 10 Tablets to a 500-mL volumetric flask, add 400 mL of Diluent, and stir for 40 minutes. Dilute with Diluent to volume, mix, and centrifuge. Quantitatively dilute an accurately measured volume (VS mL) of the clear supernatant with Diluent to obtain a solution ( VA mL) containing about 0.1 mg of fosinopril sodium per mL.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 215-nm detector and a 4.0-mm × 30-cm column that contains packing L1. The flow rate is about 2 mL per minute. Chromatograph the Resolution solution and the Standard preparation, and record the peak responses as directed for Procedure: the relative retention time is 0.4 for fosinopril related compound A, and 1.0 for fosinopril sodium; the resolution, R, between the fosinopril sodium and fosinopril related compound A peaks is not less than 2.0; and the relative standard deviation for replicate injections of the Standard preparation is not more than 2.0%.
Procedure— Separately inject equal volumes (about 50 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Continue the chromatography up to 1.5 times the retention time of the fosinopril sodium peak. Calculate the quantity, in mg, of fosinopril sodium (C30H45NNaO7P) in the portion of Tablets taken by the formula:
50C(VA / VS)(rU / rS)
in which C is the concentration, in mg per mL, of USP Fosinopril Sodium RS in the Standard preparation; VA is the volume, in mL, of the Assay preparation; VS is the volume, in mL, of supernatant taken for the Assay preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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Topic/Question Contact Expert Committee
Monograph Sujatha Ramakrishna, Ph.D.
Senior Scientific Liaison
1-301-816-8349
(SM22010) Monographs - Small Molecules 2
Reference Standards RS Technical Services
1-301-816-8129
rstech@usp.org
711 Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison
1-301-816-8106
(GCDF2010) General Chapters - Dosage Forms
USP35–NF30 Page 3283
Pharmacopeial Forum: Volume No. 33(3) Page 405