Determination of risperidone and enantiomers of 9-hydroxyrisperidone in plasma by LC-MS/MS.
A robust and validated liquid-liquid extraction LC-MS/MS method was developed for population pharmacokinetic analysis and therapeutic drug monitoring of risperidone and the enantiomers of its major active metabolite (+)-and (-)9-hydroxyrisperidone in pediatric patients. The method was rapid, sensitive and used a low sample amount (200 microL), which is very desirable for the pediatric population. The assay was validated from 0.2 to 50 ng/mL in plasma for all analytes. LLOQ for all analytes was 0.2 ng/mL. The extracts were analyzed by normal phase LC-MS/MS. The sample run time was 8 min. Intra- and interday precision for all analytes was < or =6%; method accuracy was between 89 and 99%. Additional experiments were performed to analyze matrix effects and identify a proper internal standard for each analyte. The validated method was used to study risperidone and its enantiomer metabolites in plasma as part of a population pharmacokinetic study in pediatric patients with pervasive developmental disorder (PDD).
Cabovska
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Laboratory of Applied Pharmacokinetics and Therapeutic Drug Management, Pediatric Pharmacology Research Unit, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue (MLC 6018), Cincinnati, OH 45229-3039, USA. Baiba.Cabovska@cchmc.org
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D002648:Child; D002853:Chromatography, Liquid / Q000379:methods; D006801:Humans; D007555:Isoxazoles / Q000097:blood*; D000068882:Paliperidone Palmitate; D011743:Pyrimidines / Q000097:blood*; D012015:Reference Standards; D015203:Reproducibility of Results; D018967:Risperidone / Q000097:blood*; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*
D007555:Isoxazoles; D011743:Pyrimidines; D018967:Risperidone; D000068882:Paliperidone Palmitate