(floo vox' a meen mal' ee ate).
1-Pentanone, 5-methoxy-1-[4-(trifluoromethyl)phenyl]-, O-(2-aminoethyl)oxime, (E)-, (Z)-2-butenedioate (1:1).
5-Methoxy-4¢-(trifluoromethyl)valerophenone (E)-O-(2-aminoethyl)oxime, maleate (1:1) [61718-82-9].
» Fluvoxamine Maleate contains not less than 98.0 percent and not more than 102.0 percent of C15H21F3N2O2·C4H4O4, calculated on the dried basis.
Packaging and storage Preserve in well-closed, light-resistant containers. Store at controlled room temperature.
USP Reference standards 11
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.
Melting temperature 741: between 121 and 123.
Loss on drying 731 Dry it in vacuum at 80 for 2 hours: it loses not more than 0.5% of its weight.
Residue on ignition 281: not more than 0.1%.
Heavy metals, Method II 231: 0.001%.
Buffer solution, Mobile phase, Resolution solution, and Chromatographic system Proceed as directed in the Assay.
Identification solution Dissolve a quantity of maleic acid in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 0.35 mg per mL.
Standard solution Use the Standard preparation, prepared as directed in the Assay.
Test solution Use the Assay stock preparation, prepared as directed in the Assay.
Procedure Separately inject equal volumes (about 20 µL) of the Standard solution, the Test solution, and the Identification solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the percentage of impurities in the portion of Fluvoxamine Maleate taken by the formula:
5000(C/W)F(ri / rS)in which C is the concentration, in mg per mL, of USP Fluvoxamine Maleate RS in the Standard solution; W is the weight, in mg, of Fluvoxamine Maleate used to prepare the Test solution; F is the response factor of each impurity as given in Table 1; ri is the individual peak area of each impurity in the Test solution; and rS is the peak area of fluvoxamine maleate in the Standard solution. The limits of impurities are specified in Table 1. [noteDisregard any peak due to maleic acid or the reagent blank. ]
Buffer solution Dissolve about 5 g of 1-pentanesulfonic acid sodium salt and 0.7 g of monobasic potassium phosphate in 620 mL of water. Adjust with phosphoric acid to a pH of 3.00 ± 0.05.
Mobile phase Prepare a filtered and degassed mixture of Buffer solution and acetonitrile (62:38). Make adjustments if necessary (see System Suitability under Chromatography 621).
Resolution solution Transfer about 6 mg of Fluvoxamine Maleate to a 50-mL volumetric flask. Heat the sample at 120 for 10 minutes. Cool down to room temperature, and add 3.0 mL of 0.1 N hydrochloric acid. Heat the solution in a water bath for 10 minutes. Cool down to room temperature, add 50 mg of Fluvoxamine Maleate, and dissolve in 25 mL of Mobile phase. Dilute with Mobile phase to volume, and mix.
Standard preparation Dissolve an accurately weighed quantity of USP Fluvoxamine Maleate RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 0.05 mg per mL.
Assay stock preparation Transfer an accurately weighed quantity of about 50 mg of Fluvoxamine Maleate to a 50-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix.
Assay preparation Transfer 5.0 mL of the Assay stock preparation to a 100-mL volumetric flask. Dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 234-nm detector and a 4.6-mm × 25-cm column that contains packing L7. The flow rate is about 1.7 mL per minute. The column temperature is maintained at 40. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the resolution, R, between the Z-isomer and fluvoxamine maleate is not less than 3.0 and not less than 5.0 between 5-methoxy-1-[4-(trifluoromethyl)phenyl]-1-pentanone-(E)-O-[2-[(2-succinyl)amino]ethyl]oxime and the Z-isomer. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency is not less than 5000 theoretical plates; the tailing factor is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%. [noteFor the purpose of peak identification, the approximate relative retention times are given in Table 1. ]
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 fluvoxamine maleate peaks. Calculate the quantity, in mg, of C15H21F3N2O2·C4H4O4 in the portion of Fluvoxamine Maleate taken by the formula:
1000C(rU / rS)in which C is the concentration, in mg per mL, of USP Fluvoxamine Maleate RS in the Standard preparation; and rU and rS are the peak areas obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 3272Pharmacopeial Forum: Volume No. 32(5) Page 1449