» Modafinil Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of modafinil (C15H15NO2S).
Packaging and storage Preserve in tight containers. Store at controlled room temperature.
USP Reference standards 11
Identification, Infrared Absorption 197K Grind 1 Tablet and add 50 mL each of dichloromethane and water. Shake the mixture and allow the layers to separate. Filter a portion of the lower (dichloromethane) layer and evaporate to dryness, using a stream of nitrogen if necessary. Prepare a potassium bromide pellet of the residue. To prepare the Reference Standard potassium bromide dispersion, transfer a quantity (in mg) of USP Modafinil RS, equivalent to the labeled amount of modafinil, to a suitable container, and proceed as directed above beginning with add 50 mL each of dichloromethane and water.
Medium: 0.1 N hydrochloric acid; 900 mL.
Apparatus 2: 50 rpm.
Time: 30 minutes.
Procedure Determine the amount of C15H15NO2S dissolved by employing UV absorption at the wavelength of maximum absorbance at about 222 nm on filtered portions of the solution under test, suitably diluted with Medium if necessary, in comparison with a Standard solution having a known concentration of USP Modafinil RS in the same Medium.
Tolerances Not less than 75% (Q) of the labeled amount of C15H15NO2S is dissolved in 30 minutes.
Uniformity of dosage units 905: meet the requirements.
Buffer, Mobile phase, and System suitability preparation Prepare as directed in the Assay under Modafinil. Make adjustments if necessary (see System Suitability under Chromatography 621).
Diluent Prepare as directed in the Assay.
Test solution Use the Assay preparation.
Chromatographic system (see Chromatography 621) Proceed as directed in the Assay. Chromatograph the System suitability preparation, and record the peak responses as directed for Procedure: the relative retention times are presented in the table below; the resolution, R, between modafinil and salicylic acid is not less than 1.3; and the relative standard deviation for replicate injections is not more than 2.0% based on the modafinil peak.
Procedure Inject a volume (about 5 µL) of the Test solution into the chromatograph, record the chromatogram, and measure all of the peak responses. Calculate the percentage of each impurity in the portion of Tablets taken by the formula:
100(1/F)(ri / rs)in which F is the relative response factor for an impurity (F is 0.90 for modafinil sulfone; F is 1 for all other known and unknown impurities); ri is the peak response for each impurity; and rs is the sum of the responses of all the peaks: not more than 0.5% of any individual impurity is found, not more than 0.1% of any individual unknown impurity is found, and not more than 1.5% of total impurities is found.
Buffer, Mobile phase, and System suitability preparation Prepare as directed in the Assay under Modafinil.
Diluent Prepare a mixture containing water, acetonitrile, and acetic acid (65:35:1), and mix.
Standard preparation Dissolve an accurately weighed quantity of USP Modafinil RS in Diluent, and dilute quantitatively, and stepwise if necessary, with Diluent to obtain a solution having a known concentration of about 0.4 mg per mL.
Assay preparation Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 100 mg of modafinil, to a 250-mL volumetric flask, add 200 mL of Diluent, and sonicate for about 5 minutes with intermittent manual shaking. Dilute with Diluent to volume, and mix. Pass a portion of this solution through a filter having a 0.45-µm or finer porosity, and use the filtrate.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 220-nm detector and 4.6-mm × 15-cm column that contains 5-µm packing L1. The flow rate is about 1.0 mL per minute. The column temperature is maintained at 40. Chromatograph the System suitability preparation, and record the peak responses as directed for Procedure: the relative retention times are about 1.1 for salicylic acid and 1.0 for modafinil; the resolution, R, between modafinil and salicylic acid is not less than 1.3; the tailing factor is not more than 1.5; and the relative standard deviation for replicate injections is not more than 2.0% based on the modafinil peak.
Procedure Separately inject equal volumes (about 5 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the modafinil peaks. Calculate the quantity, in mg, of modafinil (C15H15NO2S) in the portion of Tablets taken by the formula:
250C(rU / rS)in which C is the concentration, in mg per mL, of USP Modafinil 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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USP35NF30 Page 3941Pharmacopeial Forum: Volume No. 30(5) Page 1636