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


METHODS
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.


RESULTS
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.


CONCLUSIONS
The results obtained support the measurement of MPH in oral fluid as an alternative to plasma if the extended-release formulation is used.
Marchei
Emilia
E
Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanitá, Rome, Italy.
Farré
Magí
M
Pardo
Ricardo
R
Garcia-Algar
Oscar
O
Pellegrini
Manuela
M
Pacifici
Roberta
R
Pichini
Simona
S
D000328:Adult; D002853:Chromatography, Liquid; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008774:Methylphenidate / Q000031:analogs & derivatives* / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics; D012016:Reference Values; D021241:Spectrometry, Mass, Electrospray Ionization; D055815:Young Adult
D008774:Methylphenidate; C009189:ritalinic acid