(fe loe' di peen).
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C18H19Cl2NO4 384.26
3,5-Pyridinedicarboxylic acid 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-, ethyl methyl ester, (±)-.
(±)-Ethyl methyl 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate [72509-76-3; 86189-69-7].
» Felodipine contains not less than 98.0 percent and not more than 101.0 percent of C18H19Cl2NO4, calculated on the dried basis.
Packaging and storage— Preserve in tight, light-resistant containers, and store at controlled room temperature.
USP Reference standards 11
USP Felodipine RS Click to View Structure
Color of solution— Prepare a solution in methanol having a concentration of 20 mg per mL: the absorbance, determined in a 5-cm cell at the wavelength of 440 nm in a suitable spectrophotometer, methanol being used as the blank, is not greater than 0.2.
B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Loss on drying 731 Dry it at 105 for 3 hours: it loses not more than 0.5% of its weight.
Residue on ignition 281: not more than 0.1%.
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%.
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 C18H19Cl2NO4 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.
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Monograph Sujatha Ramakrishna, Ph.D.
Senior Scientific Liaison
(SM22010) Monographs - Small Molecules 2
Reference Standards RS Technical Services
USP35–NF30 Page 3154
Pharmacopeial Forum: Volume No. 27(2) Page 2144