Chiral determination of mirtazapine in human blood plasma by high-performance liquid chromatography

A method is described for the determination of the two enantiomers of mirta zapine in human blood plasma by high-performance liquid chromatography. Mea surements were performed on drug free plasma spiked with mirtazapine and us ed to prepare and validate standard curves. Levels of enantiomers of mirtaz apine were also measured in patients being treated for depression with race mic mirtazapine. Mirtazapine was separated from plasma by solid-phase extra ction using CERTIFY columns. Chromatographic separation was achieved using a Chiralpak AD column and pre-column and compounds were detected by their a bsorption at 290 nm;;;Imipramine was used as an internal standard. The assa y was validated for each analyte in the concentration range 10-100 ng/ml. T he coefficient of variance was 16% and 5.5% for(+)-mirtazapine for 10 and 1 00 ng/ml control specimens respectively and 15% and 7.3% for mirtazapine fo r 10 and 100 ng/ml control specimens respectively. This assay is appropriat e for use in the clinical range. The range of plasma mirtazapine concentrat ions from eleven patients taking daily doses of 30-45 mg of racemate was <5 to 69 ng/ml for (+)-mirtazapine and 13-88 ng/ml for (-)-mirtazapine for bl ood specimens collected 10-17.5 h after taking the dose. (C) 2000 Elsevier Science BN. All rights reserved.