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 . USP Fosinopril Related Compound A RS . USP Fosinopril Related Compound G RS .
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.
Test solution
Use portions of the solution under test passed through a 1.2-µm acrylic filter. [noteDo 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.
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
Chromatographic Column
USP32NF27 Page 2451
Pharmacopeial Forum: Volume No. 33(3) Page 405
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.
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