(moe daf' i nil).
» Modafinil contains not less than 98.0 percent and not more than 101.5 percent of C15H15NO2S, calculated on the anhydrous basis.
Packaging and storage Preserve in well-closed containers. Store at controlled room temperature.
USP Reference standards 11
Identification Infrared Absorption 197K.
Water, Method I 921: not more than 0.2%.
Residue on ignition 281: not more than 0.1%.
Heavy metals, Method I 231 Dissolve the sample in methanol and water solution (60:40): not more than 0.002%.
Buffer, Mobile phase, and System suitability preparation Prepare as directed in the Assay.
Test solution Use the Assay preparation.
Chromatographic system (see Chromatography 621) Proceed as directed under Assay. Chromatograph the System suitability preparation, and record the peak responses as directed for Procedure: the relative retention times are listed in the table below; the resolution, R, between salicylic acid and modafinil 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 Inject a volume (about 20 µL) of the Test solution into the chromatograph, record the chromatogram, and measure the peak responses. Calculate the percentage of each related compound in the portion of Modafinil 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 individual peak response of each impurity; and rs is the sum of the responses of all the peaks: not more than 0.5% of any individual known impurity is found, not more than 0.05% of any individual unknown impurity is found, and not more than 1.0% of total impurities is found.
Buffer Dissolve 6.8 g of potassium dihydrogen phosphate in 500 mL of water in a 1000-mL flask. Dilute with water to volume, and mix. Adjust with phosphoric acid to a pH of 2.3.
Mobile phase Prepare a filtered and degassed mixture of Buffer and acetonitrile (65:35). Make adjustments if necessary (see System Suitability under Chromatography 621).
Diluent Prepare a mixture containing water and acetonitrile (65:35), and mix.
System suitability preparation Dissolve suitable quantities of USP Modafinil RS and USP Salicylic Acid RS in Diluent to obtain a solution containing about 0.005 mg per mL and 0.05 mg per mL, respectively.
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 0.1 mg per mL.
Assay preparation Transfer about 100 mg of Modafinil, accurately weighed, to a 100-mL volumetric flask, dissolve in and dilute with Diluent to volume, and mix. Dilute 5.0 mL of this solution with Diluent to 50 mL, and mix well.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 220-nm detector and a 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 of the modafinil peak 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 20 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 C15H15NO2S in the portion of Modafinil taken by the formula:
1000C(rU / rS)in which 1000 is the dilution factor for the Assay preparation; 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 3940Pharmacopeial Forum: Volume No. 37(2)