Chirality in the New Generation of Antidepressants
- 1 August 2004
- journal article
- clinical trial
- Published by Ovid Technologies (Wolters Kluwer Health) in Therapeutic Drug Monitoring
- Vol. 26 (4), 366-374
- https://doi.org/10.1097/00007691-200408000-00005
Abstract
Mirtazapine is an antidepressant that acts specifically on noradrenergic and sertonergic receptors. A LC-MS method was developed that allows the simultaneous analysis of the R-(-)- and S-(+)-enantiomers of mirtazapine (MIR), demethylmirtazapine (DMIR), and 8-hydroxymirtazapine (8-OH-MIR) in plasma of MIR-treated patients. The method involves a 3-step liquid-liquid extraction, an HPLC separation on a Chirobiotic V column, and MS detection in electrospray mode. The limit of quantification (LOQ) for all enantiomers was 0.5 ng/mL, and the intra- and interday CVs were within 3.3% to 11.7% (concentration ranges 5-50 ng/mL). A method is also presented for the quantitative analysis of glucuroconjugated MIR and 8-OH-MIR. S-(+)-8-OH-MIR is present in plasma mainly as its glucuronide. Preliminary data suggest that in all patients, except in those comedicated with CYP2D6 inhibitors such as fluoxetine and thioridazine, R-(-)-MIR concentrations were higher than those of S-(+)MIR. Moreover, fluvoxamine seems also to inhibit the metabolism of MIR. Therefore, this method seems to be suitable for the stereoselective assay of MIR and its metabolites in plasma of patients comedicated with MIR and other drugs for routine and research purposes.Keywords
This publication has 13 references indexed in Scilit:
- Chiral determination of mirtazapine in human blood plasma by high-performance liquid chromatographyJournal of Chromatography B: Biomedical Sciences and Applications, 2000
- Clinical Pharmacokinetics of MirtazapineClinical Pharmacokinetics, 2000
- High-performance liquid chromatographic assay with fluorescence detection for the routine monitoring of the antidepressant mirtazapine and its demethyl metabolite in human plasmaJournal of Chromatography B: Biomedical Sciences and Applications, 1999
- MirtazapineDrugs, 1999
- Neurochemical effects of the enantiomers of mirtazapine in normal ratsEuropean Journal of Pharmacology, 1998
- A Comparison of the Physicochemical and Biological Properties of Mirtazapine and MianserinJournal of Pharmacy and Pharmacology, 1997
- In Vitro and In Vivo Studies on the Disposition of Mirtazapine in HumansClinical Drug Investigation, 1997
- MirtazapineCNS Drugs, 1996
- The α2-selective adrenoceptor antagonist org 3770 (mirtazapine, Remeron®) enhances noradrenergic and serotonergic transmissionHuman Psychopharmacology: Clinical and Experimental, 1995
- Capillary gas chromatographic assay for the routine monitoring of the antidepressant mepirzepine in human plasmaJournal of Chromatography B: Biomedical Sciences and Applications, 1987