Title
Comparison of electron and chemical ionization modes by validation of a quantitative gas chromatographic-mass spectrometric assay of new generation antidepressants and their active metabolites in plasma
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Publication type
article
Publication
Amsterdam ,
Subject
Pharmacology. Therapy
Source (journal)
Journal of chromatography: A. - Amsterdam
Volume/pages
1176(2007) :1/2 , p. 236-245
ISSN
0021-9673
ISI
000251848100029
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Abstract
A gas chromatographicmass spectrometric method (GCMS) for the simultaneous determination of the new antidepressants (mirtazapine, viloxazine, venlafaxine, trazodone, citalopram, mianserin, reboxetine, fluoxetine, fluvoxamine, sertraline, maprotiline, melitracen, paroxetine) and their active metabolites (desmethylmirtazapine, O-desmethylvenlafaxine, m-chlorophenylpiperazine, desmethylcitalopram, didesmethylcitalopram, desmethylmianserin, desmethylfluoxetine, desmethylsertraline, desmethylmaprotiline) in plasma using different ionization modes was developed and validated. Sample preparation consisted of a strong cation exchange mechanism and derivatisation with heptafluorobutyrylimidazole. The GC separation was performed in 24.8 min. Identification and quantification were based on selected ion monitoring in electron (EI) and chemical ionization (CI) modes. Calibration by linear and quadratic regression for electron and chemical ionization, respectively, utilized deuterated internal standards and a weighing factor 1/x2. Limits of quantitation were established between 5 and 12.5 ng/ml in EI and positive ionization CI (PICI), and 1 and 6.25 ng/ml in negative ionization CI (NICI). During validation stability, sensitivity, precision, accuracy, recovery, and selectivity were evaluated for each ionization mode and were demonstrated to be acceptable for most compounds. While it is clear that not all compounds can be quantitated either due to chromatographic (trazodone) or derivatisation problems (O-desmethylvenlafaxine), this method can quantitate most new antidepressants (ADs) in the therapeutic range using EI. PICI and NICI lead to higher selectivity. Moreover, NICI is of interest for small sample volumes and high sensitivity requirements. This paper draws the attention to the pros and cons of the different ionization modes in the GCMS analysis of these antidepressants in plasma.
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