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Simultaneous determination of risperidone and 9‐hydroxyrisperidone in plasma by liquid chromatography/electrospray tandem mass spectrometry
Author(s) -
Aravagiri Manickam,
Marder Stephen R.
Publication year - 2000
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/1096-9888(200006)35:6<718::aid-jms999>3.0.co;2-o
Subject(s) - chemistry , chromatography , triple quadrupole mass spectrometer , protein precipitation , electrospray ionization , electrospray , mass spectrometry , tandem mass spectrometry , selected reaction monitoring , extraction (chemistry) , elution
A simple and highly sensitive liquid chromatographic/electrospray tandem mass spectrometric (LC/MS/MS) assay was developed for the simultaneous determination of risperidone (RSP) and its major circulating metabolite 9‐hydroxyrisperidone (9‐OH‐RSP) in the plasma of humans and rats. A simple one‐step solvent extraction with 15% methylene chloride in pentane was used to isolate the compounds from plasma. The compounds were eluted from a phenyl–hexyl column and detected with a Perkin‐Elmer SCIEX API2000 triple‐quadrupole mass spectrometer using positive ion atmospheric pressure electrospray ionization and multiple reaction monitoring. The assay was linear over the range 0.1–100 ng ml −1 when 0.5 ml of plasma was used in the extraction. The overall intra‐ (within‐day) and inter‐ (between days) assay variations were < 11%. The variations in the concentrations of two long‐term quality control samples from pooled patient plasma samples analyzed over a period of 6 months were ∼10%. The analysis time for each sample was 4 min and more than 100 samples could be analyzed in one day by running the system overnight. The assay is simple, highly sensitive, selective, precise and fast. This method is being used for the therapeutic drug monitoring of schizophrenic patients treated with RSP and to study the pharmacokinetics and tissue distribution of RSP and 9‐OH‐RSP in rats. Copyright © 2000 John Wiley & Sons, Ltd.