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Correlation between methylphenidate and ritalinic acid concentrations in oral fluid and plasma.

Clinical chemistry (2010-02-20)
Emilia Marchei, Magí Farré, Ricardo Pardo, Oscar Garcia-Algar, Manuela Pellegrini, Roberta Pacifici, Simona Pichini
ABSTRACT

We studied the excretion profile of methylphenidate (MPH) and its metabolite ritalinic acid (RA) in oral fluid and plasma, the oral fluid-to-plasma (OF/P) drug ratio, and the variations of oral fluid pH after drug administration. We analyzed oral fluid and plasma samples, obtained from 8 healthy volunteers after ingestion of a single dose of 20 mg fast-release or extended-release MPH, for MPH and RA by LC-MS. We estimated the apparent pharmacokinetic parameters of MPH in plasma and oral fluid and calculated the OF/P ratio for each time interval. MPH and RA were detected in oral fluid. Whereas parent drug concentrations in oral fluid were an order of magnitude higher than those in plasma, the opposite was observed for RA. Oral fluid concentrations of MPH ranged between 0.5 and 466.7 microg/L and peaked at 0.5 h after administration of the fast-release formulation; they ranged between 0.7 and 89.5 microg/L and peaked at 2 h after administration of the extended-release formulation. Both formulations presented bimodal time-course curves for the OF/P ratio, ranging between 1.8 and 242.1 for the fast-release formulation and between 2.6 and 27.0 for extended-release. Oral fluid pH did not appear to be modified by the administration of the drug, and its influence on OF/P ratio did not affect the correlation of MPH between the 2 body fluids. The results obtained support the measurement of MPH in oral fluid as an alternative to plasma if the extended-release formulation is used.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Ritalinic acid, 99% (CP)
Supelco
Ritalinic acid hydrochloride solution, 1.0 mg/mL in methanol (as free base), ampule of 1 mL, certified reference material, Cerilliant®

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