Determination of risperidone and enantiomers of 9-hydroxyrisperidone in plasma by LC-MS/MS

Abstract

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 μL), which is very desirable for the pediatric population. The assay was validated from 0.2 -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 minutes. Intra-and interday precision for all analytes was ≤ 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).

Determination of risperidone in human plasma by HPLC-MS/MS and its application to a pharmacokinetic study in Chinese volunteers

“…The reported liquid chromatography-mass spectrometry (LC-MS) analytical method requires laborious extraction procedures like liquid-liquid extraction (Aravagiri and Marder, 2000) or solid-phase extraction (Remmerie et al, 2003), involving drying and reconstitution, long run time and high quantification limits McClean et al, 2000;Zhou et al, 2004). In recent years, several mass spectrometric methods have been developed and all have much improved sensitivity and specificity (Bhatt et al, 2006;Cabovska et al, 2007;Kousoulos et al, 2007;Moody et al, 2004).…”

Physicochemical characterization of neuroleptics. Relative stability of 7- and 9-hydroxyrisperidones and their protonated forms in gas phase and in solution

“…The pharmacological properties of 7-OH-RSP have not been investigated, thus, to avoid overestimation of 9-OH-RSP concentration, the two hydroxyl isomers need to be separated prior to their determination, as they cannot be distinguished in the usually employed mass spectrometry measurements [6]; the separation is not a straightforward matter and much effort has been made to determine risperidone and its degradation products in various substrates employing a variety of experimental techniques [7][8][9][10][11][12][13]. Knowledge of the physicochemical properties of the OH-RSP isomers may help choice and use of analytical methodologies and would probably assist further advance in pharmacokinetics understanding of both isomers.…”

Simultaneous determination of risperidone and 9-hydroxyrisperidone enantiomers in human blood plasma by liquid chromatography with electrochemical detection

“…Recently two LC-MS/MS methods for simultaneous quantification of RISP and 9-OH-RISP enantiomers using Chiralcel OJ chiral column were published [28,29]. Both of these methods used a low sample amount (200 L), were rapid, and sensitive (LLOQ for all analytes was 0.2 ng/mL).…”