Quantification of eight new antidepressants and five of their active metabolites in whole blood by high-performance liquid chromatography-tandem mass spectrometry.
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.
Castaing
Nadège
N
Department of Clinical Pharmacology and Toxicology, Pellegrin Hospital and University Victor Segalen, 33076 Bordeaux, France.
Titier
Karine
K
Receveur-Daurel
Mathilde
M
Le-Déodic
Maité
M
Le-bars
Delphine
D
Moore
Nicholas
N
Molimard
Mathieu
M
D000928:Antidepressive Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D053593:Forensic Toxicology; D006801:Humans; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry
D000928:Antidepressive Agents