AbstractA crossover study in 18 subjects evaluated the plasma concentration–time profile of two different 20 mg sustained‐release (SR) methylphenidate (MPH) tablets administered before breakfast, compared to a 10 mg immediate‐release (IR) tablet administered before breakfast and again 5 h later, before lunch. Plasma MPH concentrations were determined using a sensitive and precise gas chromatography–mass spectrometry method, incorporating a deuterated internal standard. The mean peak MPH concentration was 6.4 ng ml−1 for the IR product versus 4·6 ng ml−1 and 4·8 ng ml−1 for the two SR formulations. Peak concentrations occurred at 3·3 h after dosing with the SR products, compared to 1·5 h after the first dose of the IR product. The extent of absorption for the three products, as determined from areas under the plasma concentration‐time curves, were within 5 per cent of each other. There was no significant difference in rate or extent of absorption between the two SR formulations.