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Published:
Journal of Analytical Toxicology,
ISSN 0146-4760,
Volume 31, Number 6, July/August,
pp.334-341
Quantification of Eight New Antidepressants
and Five of their Active Metabolites in Whole Blood by High-Performance
Liquid Chromatography–Tandem Mass Spectrometry
Nadège Castaing, Karine Titier,
Mathilde Receveur-Daurel, Maité Le-Déodic, Delphine
Le-bars, Nicholas Moore, and Mathieu Molimard
Department of Clinical Pharmacology and Toxicology, Pellegrin
Hospital and University Victor Segalen, 33076 Bordeaux, France
A liquid chromatography–tandem mass spectrometry
method is described for the blood determination of selective
serotonin reuptake inhibitors (fluoxetine, paroxetine, sertraline,
fluvoxamine, and citalopram), serotonin noradrenaline reuptake
inhibitors (milnacipram and venlafaxine), a noradrenergic and
specific serotoninergic antidepressant (mirtazapine) and five
of their active metabolites (norfluoxetine, desmethylcitalopram,
didesmethylcitalopram, desmethylvenlafaxine, and desmethylmirtazapine).
After a liquid–liquid extraction from blood, the compounds
and the internal standard (methylrisperidone) were eluted on
a XTerra® RP18 column with a gradient of acetonitrile/ammonium
formate buffer 4 mmol/L pH 3.2. They were then detected by electrospray
ionization mass spectrometry with multiple reaction monitoring
mode. The calibration curves were linear over the range 5–500
ng/mL (20–2000 ng/mL for venlafaxine and desmethylvenlafaxine).
The limit of quantification was set at 5 ng/mL for each compound
(except for venlafaxine and desmethylvenlafaxine: 20 ng/mL).
The bias were lower than 12%. Intraday and interday precisions,
expressed as variation coefficient, were lower than 11%. The
extraction recoveries were between 70 and 90% except for desmethylmirtazapine,
desmethylvenlafaxine, milnacipram, and didesmethylcitalopram.
This specific and sensitive method allows management of intoxication
and is suitable for the routine determination of antidepressants
in forensic investigations.
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