Chromatographic purity—
Mobile phase, Standard preparation, Resolution solution, and Chromatographic system—
Proceed as directed in the Assay.
Test preparation—
Use the Assay preparation.
Procedure—
Inject a volume (about 40 µL) of the
Test preparation into the chromatograph. Allow the
Test preparation to elute for not less than two times the retention time of felodipine. Record the chromatograms, and measure the areas for the impurity peaks. Calculate the percentage of each impurity in the portion of Felodipine taken by the formula:
100(ri / rs),
in which
ri is the peak response for each impurity; and
rs is the sum of all the responses of all the peaks: not more than 1.0% of any individual impurity is found, and the sum of all impurities is not more than 1.5%.
Assay—
Mobile phase—
Dissolve 6.9 g of monobasic sodium phosphate in 400 mL of water in a 1-liter volumetric flask. Add 8.0 mL of 1 M phosphoric acid, dilute with water to volume, and mix. Prepare a filtered and degassed mixture of this solution, acetonitrile, and methanol (40:40:20). Make adjustments if necessary (see
System Suitability under
Chromatography 
621
).
Resolution solution—
Dissolve 150 mg of Felodipine in a mixture of 25 mL of tertiary butyl alcohol and 25 mL of 1 N perchloric acid, add 10 mL of 0.1 M ceric sulfate, mix, and allow to stand for 15 minutes. Add 3.5 mL of 10 N sodium hydroxide, and neutralize with 2 N sodium hydroxide. Shake the mixture with 25 mL of methylene chloride in a separator. Draw off the lower layer, and evaporate it to dryness under a stream of nitrogen on a water bath. Dissolve 10 mg of the residue (felodipine oxidation product) and 5 mg of
USP Felodipine RS in
Mobile phase, dilute with
Mobile phase to 100 mL, and mix. Transfer 1.0 mL of the resulting solution to a 100-mL volumetric flask, dilute with
Mobile phase to volume, and mix.
Standard preparation—
Dissolve an accurately weighed quantity of
USP Felodipine RS in
Mobile phase, and quantitatively dilute with
Mobile phase to obtain a solution having a known concentration of about 0.3 mg per mL.
[NOTE—Prepare this solution fresh prior to analysis.
]
Assay preparation—
Transfer an accurately weighed quantity of about 30 mg of Felodipine to a 100-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix. [NOTE—Prepare this solution fresh prior to analysis.]
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L1. The flow rate is about 1 mL per minute. Chromatograph the
Standard preparation, and record the peak responses as directed for
Procedure: the capacity factor,
k¢, is not less than 5.0; the column efficiency is not less than 1500 theoretical plates; and the tailing factor is not greater than 1.5. Inject 20 µL of the
Resolution solution into the chromatograph, and adjust the sensitivity of the system so that the heights of the two peaks in the chromatogram are not less than 20% of recorder full scale. The resolution,
R, between the first peak (felodipine oxidation product) and the second peak (felodipine) is not less than 2.5.
Procedure—
Separately inject equal volumes (about 40 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 C
18H
19Cl
2NO
4 in the portion of Felodipine taken by the formula:
100C(rU / rS),
in which
C is the concentration, in mg per mL, of
USP Felodipine RS in the
Standard preparation; and
rU and
rS are the peak responses obtained from the
Assay preparation and the
Standard preparation, respectively.
;)
for 3 hours: it loses not more than 0.5% of its weight.