Liquid chromatography-tandem mass spectrometry method for determination of five antidepressants and four atypical antipsychotics and their main metabolites in human serum
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- 作者：Romana U?inovsk¨¢ ; Hana Brozmanov¨¢ ; Pavel ?i?t¨ªk ; Petr ?ilh¨¢n ; Ivana Kac¨ª?ov¨¢ ; Karel Lemr ; Milan Grundmann
- 关键词：Psychotropic drugs ; Therapeutic drug monitoring ; High performance liquid chromatography ; Mass spectrometry
- 刊名：Journal of Chromatography B, Analytical Technologies in the Biomedical and Life Sciences
- 出版年：2012
- 出版时间：15 October, 2012
- 年：2012
- 卷：907
- 期：Complete
- 页码：101-107
- 全文大小：468 K
文摘
The rapid and simple ultra performance liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination parent drugs: sertraline, fluoxetine, citalopram, paroxetine, venlafaxine, clozapine, olanzapine, quetiapine, risperidone, and their active and nonactive metabolites N-desmethylsertraline, norfluoxetine, desmethylcitalopram, didemethylcitalopram, N-desmethylvenlafaxine, O-desmethylvenlafaxine, N-desmethylclozapine, N-desmethylolanzapine, 2-hydroxyolanzapine and 9-hydroxyrisperidone in human serum. Precipitation of serum proteins was performed with a precipitation reagent consisting of 0.05 % solution of ZnSO4¡¤7H2O in acetonitrile/methanol (40:60, v/v). Alprenolol was used as an internal standard. Chromatographic separation was carried out on a BEH C18 column using gradient elution mobile phase A (2 mmol/L ammonium acetate, 0.1 % formic acid in 5 % acetonitrile, v/v/v) and B (2 mmol/L ammonium acetate, 0.1 % formic acid in 95 % acetonitrile, v/v/v). Electrospray in positive mode was used for ionization. Detection was performed on a triple-quadrupole tandem mass spectrometer by multiple reaction monitoring. Analysis time was 5 min. Drugs were separated into three groups with low, medium and high levels. Correlation coefficients of calibration curves were in the range 0.995-1.000. Coefficients of variation were 4.2-9.5 % for intra-assay and 3.0-11.9 % for inter-assay. Recoveries were 87.1-110 % for intra-assay and 88.1-108.2 % for inter-assay. The method was fully validated and can be successfully applied for routine analyses.