Fenoprofen Calcium
(fen'' oh proe' fen kal' see um).
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C30H26CaO6·2H2O 558.63

Benzeneacetic acid, -methyl-3-phenoxy-, calcium salt dihydrate, (±)-.

Calcium (±)-m-phenoxyhydratropate dihydrate [53746-45-5].

Anhydrous 522.61 [34597-40-5].
» Fenoprofen Calcium contains not less than 97.0 percent and not more than 103.0 percent of (C15H13O3)2Ca, calculated on the anhydrous basis.
Packaging and storage— Preserve in tight containers.
USP Reference standards 11
USP Fenoprofen Calcium RS Click to View Structure
Identification—
B: Heat a 1 in 50 mixture of it with acetic acid, filter, and add 2 mL of ammonium oxalate TS to the filtrate: a white precipitate, which is soluble in 3 N hydrochloric acid, is formed.
Water, Method I 921: between 5.0% and 8.0%.
Chromatographic purity—
Solution A— Prepare a filtered and degassed mixture of water and acetic acid (98:2).
Solution B— Prepare a filtered and degassed mixture of acetonitrile and acetic acid (98:2).
Mobile phase— Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).
Diluent: a mixture of water and acetonitrile (1:1).
System suitability solution— Dissolve accurately weighed quantities of 3-phenoxybenzoic acid and USP Fenoprofen Calcium RS in Diluent to obtain a solution containing about 0.02 mg of each per mL.
Standard solution— Dissolve an accurately weighed quantity of USP Fenoprofen Calcium RS in Diluent to obtain a solution having a known concentration of about 0.02 mg per mL.
Test solution— Transfer about 200 mg of Fenoprofen Calcium, accurately weighed, to a 100-mL volumetric flask, dissolve in and dilute with Diluent to volume, and mix.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 270-nm detector and a suitable 4.6-mm × 25-cm column1 that contains 5-µm packing L7. The flow rate is 1.5 mL per minute. The chromatograph is programmed as follows.
Time
(minutes)
Solution A
(%)
Solution B
(%)
Elution
0 70 30 equilibration
0–3 70 30 isocratic
3–41 70®10 30®90 linear gradient
41–42 10 90 isocratic
42–43 10®70 90®30 linear gradient
43–55 70 30 re-equilibration
Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.89 for 3-phenoxybenzoic acid and 1.0 for fenoprofen; the resolution, R, between 3-phenoxybenzoic acid and fenoprofen is not less than 9.0; and the tailing factor for the fenoprofen peak is not more than 2.0. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the tailing factor for the fenoprofen peak is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentage of each impurity in the portion of Fenoprofen Calcium taken by the formula:
10,000(C/W)(ri /rS)
in which C is the concentration, in mg per mL, of USP Fenoprofen Calcium RS in the Standard solution; W is the quantity, in mg, of Fenoprofen Calcium taken to prepare the Test solution; ri is the response for each impurity peak obtained from the Test solution; and rS is the response of the fenoprofen peak obtained from the Standard solution: not more than 0.5% of any individual impurity is found; and not more than 2.0% of total impurities is found.
Content of calcium—
Test solution— Transfer about 750 mg of Fenoprofen Calcium, accurately weighed, to a 50-mL volumetric flask, dissolve in alcohol with the aid of heat, if necessary, cool, dilute with alcohol to volume, and mix.
Procedure— In a 150-mL beaker, mix 70 mL of water, 2 mL of sodium hydroxide solution (1 in 10), and about 0.3 g of hydroxy naphthol blue. Add about 1 mL of the Test solution, and titrate to the blue endpoint with 0.05 M edetate disodium. Transfer 10.0 mL of the Test solution to the solution so obtained, and titrate to the blue endpoint with 0.05 M edetate disodium VS. Each mL of 0.05 M edetate disodium is equivalent to 2.004 mg of Ca: not less than 7.3% and not more than 8.0% of Ca, calculated on the anhydrous basis, is found.
Assay—
Mobile phase— Prepare a suitable degassed mixture of acetonitrile, water, and phosphoric acid (50:49.6:0.4). Make adjustments if necessary (see System Suitability under Chromatography 621).
Diluting solution— Prepare a mixture of methanol and water (700:300).
Resolution solution— Prepare a solution in Diluting solution containing about 1 mg of Fenoprofen Calcium and 1 mg of gemfibrozil per mL.
Standard preparation— Transfer about 70 mg of USP Fenoprofen Calcium RS, accurately weighed, to a 100-mL volumetric flask, add 0.5 mL of 0.5 N hydrochloric acid and 2 mL of acetone, and dissolve by shaking. Dilute with Diluting solution to volume, and mix.
Assay preparation— Transfer about 70 mg of Fenoprofen Calcium, accurately weighed, to a 100-mL volumetric flask, add 0.5 mL of 0.5 N hydrochloric acid and 2 mL of acetone, and dissolve by shaking. Dilute with Diluting solution to volume, and mix.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 272-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L7. The flow rate is about 2 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.5 for fenoprofen and 1.0 for gemfibrozil; the tailing factor for the fenoprofen peak is not more than 2; and the resolution, R, between the fenoprofen peak and the gemfibrozil peak is not less than 8. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency determined from the fenoprofen peak is not less than 3000 theoretical plates; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of (C15H13O3)2Ca in the portion of Fenoprofen Calcium taken by the formula:
100C(rU / rS)
in which C is the concentration, in mg per mL, of anhydrous fenoprofen calcium in the Standard preparation, as determined from the concentration of USP Fenoprofen Calcium RS, corrected for moisture content by a titrimetric water determination; and rU and rS are the fenoprofen peak responses obtained from the Assay preparation and the Standard preparation, respectively.

1  One suitable column brand is the Zorbax Eclipse XDB-C8.
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Monograph Clydewyn M. Anthony, Ph.D.
Senior Scientific Liaison
1-301-816-8139
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