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Liquid chromatography/tandem mass spectrometry method for simultaneous determination of risperidone and its active metabolite 9‐hydroxyrisperidone in human plasma
Author(s) -
Bhatt Jignesh,
Subbaiah Gunta,
Singh Sadhana
Publication year - 2006
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.2537
Subject(s) - chemistry , chromatography , protein precipitation , mass spectrometry , analyte , tandem mass spectrometry , liquid chromatography–mass spectrometry , metabolite , extraction (chemistry) , active metabolite , biochemistry
A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method has been developed and validated for simultaneous quantification of risperidone (RSP) and its active metabolite 9‐hydroxyrisperidone (9‐OH‐RSP) in human plasma. The analytes were extracted from human plasma by using the protein precipitation extraction technique. Methyl risperidone was used as internal standard for RSP and 9‐OH‐RSP. A Betasil C18 column provided chromatographic separation of analytes followed by detection with mass spectrometry. The mass transition ion‐pair was followed as m/z 411.28 → 191.15 for RSP and m/z 427.30 → 207.10 for 9‐OH‐RSP. The method involves a simple extraction, isocratic chromatography conditions and mass spectrometric detection that enable detection at sub‐nanogram levels. The proposed method has been validated with a linear range of 0.10–15.0 ng/mL for RSP and 9‐OH‐RSP. The intrarun and interrun precision and accuracy values were within 15%. The overall recoveries for RSP and 9‐OH‐RSP were 82.1% and 83.2%, respectively. The total analysis time was as low as 3.0 min only. The developed method was applied for the determination of the pharmacokinetic parameters of RSP and 9‐OH‐RSP following a single oral administration of a 1 mg RSP tablet in 24 healthy male volunteers. Copyright © 2006 John Wiley & Sons, Ltd.