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Clinical Chemistry 20: 440-443, 1974;
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Clinical Chemistry, Vol 20, 440-443, Copyright © 1974 by the American Association for Clinical Chemistry

Gas-Liquid Chromatographic Procedure for Measurement of Methylphenidate Hydrochloride and Its Metabolite, Ritalinic Acid, in Urine

Rhondda Wells 1, Keith B. Hammond 1, and Denis O. Rodgerson 1

1 Pediatric Microchemistry Laboratory, Univ. of Colorado Medical Center, Denver, Colo. 80220.

A gas-liquid chromatographic procedure has been developed for measuring methylphenidate and its metabolite, ritalinic acid, in urine. The unchanged drug is extracted into chloroform from alkalinized urine together with an internal standard, diphenhydramine. The solvent is removed, the residue dissolved in ethanol, and aliquots are injected into a gas-chromatographic column containing 3% OV-17. Ritalinic acid is recovered from the urine by lyophilizing the aqueous phase remaining after the unchanged methylphenidate is extracted into chloroform. The ritalinic acid is methylated with diazomethane to form methylphenidate, which is then assayed as described. Recovery of methylphenidate added to normal urine was quantitative and reproducible (CV, 3.2%). Ritalinic acid added to drug-free urine was recovered with an efficiency of 90-98%, but somewhat less reproducibly (CV, 12.8%). No interfering substances were found in normal urines. Between 35-98% of a single therapeutic (10 mg) dose given to hyperkinetic children could be recovered from the urine collected during the 6 h immediately after the dose. Only a small proportion was excreted as the unchanged drug (0.8-11.0%), the remainder being excreted as ritalinic acid.


Key Words: drug metabolism • treatment of drug-induced lethargy and of hyperkinesis

Submitted on December 12, 1973
Accepted on January 24, 1974






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Copyright © 1974 by the American Association for Clinical Chemistry.