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