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Determination of risperidone and 9‐Hydroxyrisperidone using HPLC, in plasma of children and adolescents with emotional and behavioural disorders
Author(s) -
Jones Tanya,
Van Breda Karin,
Charles Bruce,
Dean Angela J.,
McDermott Brett M.,
Norris Ross
Publication year - 2009
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.1204
Subject(s) - chemistry , risperidone , chromatography , high performance liquid chromatography , active metabolite , detection limit , metabolite , psychology , biochemistry , schizophrenia (object oriented programming) , psychiatry
A simple, rapid, selective, accurate and precise method is described for the determination of risperidone and its active metabolite, 9‐hydroxyrisperidone, in plasma using a chemical derivative of risperidone (methyl‐risperidone) as the internal standard. The sample workup involved a single‐step extraction of 1 mL plasma, buffered to pH 10, with heptane–isoamyl alcohol (98:2 v/v), then evaporation of the heptane phase and reconstitution of the residue in mobile phase. HPLC separation was carried out at on C 18 column using a mobile phase of 0.05 m dipotassium hydrogen orthophosphate (containing 0.3% v/v triethylamine) adjusted to pH 3.7 with orthophosphoric acid (700 mL), and acetonitrile (300 mL). Flow rate was 0.6 mL/min and the detection wavelength was 280 nm. Retention times were 2.6, 3.7 and 5.8 min for 9‐hydroxy risperidone, risperidone and the internal standard, respectively. Linearity in spiked plasma was demonstrated from 2 to 100 ng/mL for both risperidone and 9‐hydroxyrisperidone ( r ≥ 0.999). Total imprecision was less than 13% (determined as co‐efficient of variation) and the inaccuracy was less than 12% at spiked concentrations of 5 and 80 ng/mL. The limit of detection, determined as three times the baseline noise, was 1.5 ng/mL. Clinical application of the assay was demonstrated for analysis of post‐dose (0.55–4.0 mg/day) samples from 28 paediatric patients (aged 6.9–17.9 years) who were taking risperidone orally for behavioural and emotional disorders. Copyright © 2009 John Wiley & Sons, Ltd.