Determination of risperidone and 9-hydroxyrisperidone in human plasma by liquid chromatography: application to the evaluation of CYP2D6 drug interactions.
A high-pressure liquid chromatography with ultra-violet detection method for the simultaneous determination of risperidone and 9-hydroxyrisperidone in plasma after liquid-liquid extraction has been developed. The limit of quantitation was 5 nmol/L, and the inter-day coefficient of variation was less than 8% for both compounds. The mean recoveries of risperidone and 9-hydroxyrisperidone added to plasma were 96.8 and 99.4%, with an intra-day coefficient of variation of under 5 and 6%, respectively. Studies of analytical interference showed that the most commonly co-administered antidepressants and benzodiazepines did not interfere. The method was used for the determination of the plasma concentrations of a schizophrenic patient treated daily with an oral dose of 4.5 mg risperidone. The patient suffered severe extrapyramidal side-effects after adding risperidone to his previous medication of haloperidol and levomepromazine. The risperidone plasma concentration was well above the average (182 nmol/L), which suggests that a pharmacokinetic interaction occurred, presumably due to inhibition of the enzyme CYP2D6.
LLerena
Adrián
A
Department of Pharmacology, Faculty of Medicine, University of Extremadura, Avda. de Elvas s/n, 06071, Badajoz, Spain. allerena@unex.es
Berecz
Roland
R
Dorado
Pedro
P
de la Garza
César Sanz
CS
Norberto
Maria Jesús
MJ
Cáceres
Macarena
M
Gutiérrez
José Ramón
JR
D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood*; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D004347:Drug Interactions; D006801:Humans; D007555:Isoxazoles / Q000097:blood*; D008297:Male; D000068882:Paliperidone Palmitate; D011743:Pyrimidines / Q000097:blood*; D015203:Reproducibility of Results; D018967:Risperidone / Q000097:blood*
D014150:Antipsychotic Agents; D007555:Isoxazoles; D011743:Pyrimidines; D019389:Cytochrome P-450 CYP2D6; D018967:Risperidone; D000068882:Paliperidone Palmitate