Gas chromatographic/mass spectrometric analysis of methylphenidate (ritalin) in serum.

A gas chromatographic/mass spectrometric (GG/MS) procedure for the determination of methylphenidate in 1 mL of serum or plasma is reported employing ethylphenidate as internal standard. A 50/50 (V/V) mixture of benzene and hexane is used to extract the methylphenidate and ethylphenidate from plasma. After evaporation of solvent the residue is redissolved in 50 microL hexane. Methyl- and ethylphenidate are then derivatized by the addition of 50 ML of trifluoroacetic anhydride and the TFA derivatives are injected into a quadrupole GC/MS for analysis. This method has a lower limit of sensitivity for methylphenidate of 2.0 micrograms/L. The between-day precision study yielded coefficients of variation of 10.4% and 14.8% at methylphenidate concentrations of 25.6 and 5.2 micrograms/L respectively. The assay has been used to investigate the pharmacokinetics of methylphenidate administered to 6 children for treatment of hyperkinesis. The study yielded ranges for volume of distribution, elimination half-life, and total body clearance of 5.0-6.8 L/kg, 1.6-2.7 hours, and 1.4-2.9 L/kg-hr respectively.