Modafinil
Acetamide, 2-[(diphenylmethyl)sulfinyl]-. 2-[(Diphenylmethyl)sulfinyl]-acetamide [68693-11-8]. » 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.
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%.
Related compounds
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.
Assay
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.
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
Chromatographic Column
USP32NF27 Page 2995
Pharmacopeial Forum: Volume No. 30(5) Page 1634
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.
|