Simultaneous analysis of olanzapine, fluoxetine, and norfluoxetine in human plasma using liquid chromatography-mass spectrometry and its application to a pharmacokinetic study.
J Chromatogr B Analyt Technol Biomed Life Sci
; 1092: 506-514, 2018 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-30008307
ABSTRACT
Adjunctive therapy with olanzapine and fluoxetine has been shown to be beneficial in treatment-resistant depression and the depressive phase of bipolar disorder. Consensus guidelines issued by the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie strongly recommend that patients taking olanzapine undergo therapeutic drug monitoring (TDM), and suggest that TDM is useful for patients taking fluoxetine. The aim of the current study was to develop and validate a sensitive, practical, and robust liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for simultaneous determination of olanzapine, fluoxetine, and norfluoxetine in human plasma for routine TDM. Simple liquid-liquid extraction using ethyl acetate was used to extract olanzapine, fluoxetine, and norfluoxetine from 200⯵L of pre-basified human plasma. Analytes were separated on an Agilent Eclipse Plus C18 column (4.6â¯×â¯100â¯mm, 5⯵m) eluted with a mobile phase consisting of methanol20â¯mM ammonium formate buffer (82.517.5, v/v), and then quantified using an electrospray ionization source operated in positive ion multiple reaction monitoring mode. The linear range for the analytes was 0.2-25â¯ng/mL, covering the vast majority of levels encountered in real-life samples. A weighting factor of 1/x2 best fit the calibration curves. The mean internal standard-normalized matrix effects for all analytes were 99.5%-110%. The extraction recoveries were 75%-85% for olanzapine and olanzapined3, and 58%-69% for fluoxetine, norfluoxetine, and their deuterated internal standards. Accuracy and precision values also met the acceptance criteria. The stability assessments showed that QC samples containing the three analytes were stable for at least 1â¯d at room temperature, 21â¯d at -70⯰C, and through three freeze-thaw cycles. Post-preparation storage for 2â¯d in the autosampler did not cause obvious degradation of the investigated compounds. This validated high performance LC-MS/MS method was successfully applied to a pharmacokinetic study in healthy male volunteers.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Espectrometria de Massas
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Benzodiazepinas
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Fluoxetina
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Cromatografia Líquida
Tipo de estudo:
Diagnostic_studies
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Guideline
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Prognostic_studies
Limite:
Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article