Therapeutic drug monitoring of mirtazapine, desmethylmirtazapine, 8-hydroxymirtazapine, and mirtazapine-N-oxide by enantioselective HPLC with fluorescence detection.

摘要

The tetracyclic antidepressant mirtazapine has been in clinical use for several years as a racemic drug. Because of a relatively narrow therapeutic index, therapeutic drug monitoring may be helpful to individually optimize therapy with mirtazapine. An enantioselective high-performance liquid chromatography (HPLC) method with fluorescence detection has been developed for the quantification of mirtazapine, desmethyl mirtazapine, 8-hydroxy mirtazapine, and mirtazapine N-oxide. The method is suitable for the analysis of plasma and urine samples in the range from 1 to 100 ng/mL with precision (coefficient of variation, or CV) between 12% and 19%. The sample preparation step comprises a liquid-solid extraction procedure with good recoveries, between 85% and 99%. Patient samples for therapeutic drug monitoring as well as concentration-time series were assayed and the resulting enantiomer ratios analyzed. Typical trough levels were between 1 and 100 ng/mL, with enantiomer ratios of approximately 0.42 (S/R). Inconcentration-time series, enantiomer ratios distinctively greater than 1 were observed at early time points. Because the enantiomers of mirtazapine and desmethyl mirtazapine have different pharmacological properties, the method is believed to be helpful in understanding the concentration-effect relationships in the former.