Modafinil

C15H15NO2 S                                                                                Mol.Wt. 273.4

Modafinil is acetamide, 2-[(diphenylmethyl)sulphenyl]; 2-[( Diphenylmethyl)sulfinyl]-acetamide.

Modafinil contains not less than 98.0 per cent and not more than 101.5 per cent of C15H15NO2 S, calculated on the anhydrous basis.

Category. Narcolepsy and sleep disorders.

Dose.200 mg orally once a day in the morning.

Description.  A white to off-white, crystalline powder.

Identification

    Determine by infrared absorption spectrophotometry (2.4.6). Compare the spectrum

     with that obtained with modafinil RS or with the reference spectrum of modafinil. 

Tests

Related substances. Determine by liquid chromatography (2.4.14), as described under Assay with the following modifications.

Name                                              Relative             Correction

                                                    retention time            factor

Modafinil                                           1.0                       ---

Salicylic acid1                                    1.1                       ---

Modafinil acid²                                                  1.4                       __

Modafinil sulphone3                                     1.7                      1.1

Modafinil ester4                                 3.0                       __

1 salicylic acid is used for calculating resolution and is not a potential impurity,

2 2-[(diphenylmethyl)sulphenyl]acetic acid,

3 2-[(diphenylmethyl)sulphonyl]acetamide,

4 2-[(diphenylmethyl)sulphenyl]acetic acid methyl ester.

Inject reference solution (a). The test is not valid unless the resolution between the peaks due to modafinil and salicylic acid is not less than 1.3 and the tailing factor for modafinil peak is not more than 1.5.

Inject the test solution. . The area of the peak due to impurity of modafinil acid, modafinil sulphone and modafinil ester is not more than 0.5 per cent each, the area of any other secondary peak is not more than 0.05 per cent and the sum of areas of all the secondary peaks is not more than 1.0 per cent, calculated by area normalisation.

Water (2.3.43). Not more than 0.2 per cent.

Sulphated ash (2.3.18). Not more than 0.1 per cent.

Assay. Determine by liquid chromatography (2.4.14).

Solvent mixture. A mixture of 35 volumes of acetonitrile and 65 volumes of water.

Test solution. Dissolve 50 mg of the substance under examination in 50.0 ml with solvent mixture. Dilute 5.0 ml of this solution to 50.0 ml with the same solvent.

Reference solution (a). A 0.0005 per cent w/v solution of modafinil RS and 0.001 per cent w/v solution of salicylic acid in the solvent mixture.

Reference solution (b). A 0.01 per cent w/v solution of modafinil RS in solvent mixture.

Chromatographic system

     –   a stainless steel column 15 cm x 4.6 mm, packed with octadecylsilane bonded to porous silica (5 µm),

     –   column temperature: 40°,

     –   mobile phase: a mixture of 35 volumes of acetonitrile and 65 volumes of buffer solution prepared by dissolving 6.8 g of potassium dihydrogen phosphate in 900 ml of water, adjusted the pH to 2.3 with orthophosphoric acid and diluting to 1000 ml with water.

     –   flow rate: 1 ml per minute,

     –   spectrophotometer set at 220 nm,

     –   injection volume: 20 µl.

The relative retention time of modafinil and salicylic acid peak with reference to modafinil peak is about 1.1.

Inject reference solution (a). The test is not valid unless the resolution between the peaks due to modafinil and salicylic acid is not less than 1.3, the tailing factor for modafinil peak is not more than 1.5 and the relative standard deviation of replicate injections is not more than 2.0 per cent.

Inject the test solution and reference solution (b).

Calculate the content of C₁₅H₁₅NO₂S.

Storage. Preserve in well-closed containers. Store at controlled room temperature.