Development and validation of a reversed phase liquid chromatographic method for separation and determination of related-substances of modafinil in bulk drugs

A reversed-phase high-performance liquid chromatographic (RP-HPLC) method for determination and evaluation of purity of modafinil in bulk drugs using Kromasil C18 column with acetonitrile: 0.02 M ammonium acetate as a mobile phase in gradient elution mode at 30 °C and detection at 225 nm using photodiode array detector has been developed. The effects of pH, temperature and the percent of organic modifier on resolution were studied. Related substances, viz, sulphide, sulphoxide, sulphones of the modafinil, acid and ester derivatives, were separated and quantified. The method was found to be simple, rapid, selective and capable of detecting all process related impurities at trace levels in the finished products of modafinil with detection limits of 0.6–2.4 × 10−8 g. The method was validated with respect to accuracy, precision, linearity, ruggedness, and limits of detection and quantification. It was found to be suitable not only for monitoring the reactions during the process development but also quality assurance of modafinil.