Development and validation of an analytical method for quantification of 15 non-tricyclic antidepressants in serum with UPLC-MS/MS

摘要: Objective Non-tricyclic antidepressants are often encountered in overdose cases, and for some of them therapeutic monitoring might be warranted [1] . Therefore we developed validated an ultra-performance liquid chromatography-tandem mass spectrometry method the quantification 15 common non-tricyclic serum: citalopram, desmethylcitalopram, desmethylfluoxetine, desmethylvenlafaxine, duloxetine, fluoxetine, fluvoxamine, melitracen, mianserin, mirtazapine, paroxetine, reboxetine, sertraline, trazodone venlafaxine. The selected pharmaceuticals represent (nor) tramadol (added because desmethylvenlafaxine interference) all available Belgium. Methods Serum samples (250 μL) were precipitated with methanol acetonitrile containing 5 ng internal standards: mirtazapine-D4, paroxetine-D5, reboxetine-D6 venlafaxine-D6. supernatant was evaporated at 56 °C under a flow nitrogen reconstituted 100 μL 50:50 methanol:water 2 mM ammonium acetate. Five microliters injected target analytes separated on 100 × 2.1 mm ACQUITY BEH C18 column (Waters, Zellik, Belgium) using Waters Ultra-Performance Liquid Chromatography system. eluted within 7.5 min, gradient acetate 0.1% formic acid water rate 0.4 mL/min. Quantification performed triple quadrupole TQD multiple reaction (MRM) positive mode (2 MRMs per analyte). A six-point calibration curve used to cover large concentration range from 10 ng/mL 1000 ng/mL. based Scientific Working Group Forensic Toxicology (SWGTOX) guideline. Results No interfering signals matrix, standard or tricyclic antidepressant drugs found. Limits limits detection ranged 10 85 ng/mL 2.0 28 ng/mL, respectively. Ion suppression matrix effects varied 36 108% compounds 47 102% standards. Process efficiency 22 106%. Intra- interassay imprecision 3.5 12.3% 3.1 12.3%, bias assay lower than 15% compounds, except lowest concentrations (bias  Conclusion Good validation performance obtained thanks use deuterated standards that adjusted compensate global variability. This is therefore suitable both drug suspected cases.