Quantitative determination of d- and l-threo enantiomers of methylphenidate in brain tissue by liquid chromatography-mass spectrometry

Abstract

Methylphenidate, a psychostimulant used for the treatment of attention deficit hyperactivity disorder and narcolepsy, is administered as a 50:50 racemic mixture, despite the fact that d-methylphenidate has been shown to have greater pharmacologic activity. This paper presents a validated LC-MS/MS approach to separation and quantification of methylphenidate enantiomers using a vancomycin column and triethylammonium acetate to enhance the chiral separation. The method is applicable to the monitoring of these enantiomers in mouse brain, with a limit of detection of 0.5 ng/mL and a lower limit of quantification of 7.5 ng/mL. © 2013 John Wiley & Sons, Ltd.