Measurement of total mirtazapine and normirtazapine in plasma/serum by liquid chromatography with fluorescence detection.
A simple high performance liquid chromatography (HPLC) method for the measurement of the new antidepressant mirtazapine and its N-demethyl metabolite, normirtazapine, in human plasma or serum during low dose mirtazapine therapy has been developed. A Waters Spherisorb S5 SCX column was used with ammonium perchlorate (50 mmol/l) in methanol/water (95 + 5 (v/v)), apparent pH 6.7, as eluent, and fluorescence detection. Only small volumes of sample (0.2 ml) and extraction solvent are used. An interference study found no significant co-elution with drug or metabolite, although paroxetine co-elutes with the internal standard. The recovery of mirtazapine and normirtazapine (mean +/- S.D.) was 79 +/- 2, and 64 +/- 3%, respectively. The LOD was estimated as 0.5 microg/l, LLOQ was 1 microg/l, with a linear response over the concentration range 4-1000 microg/l (both analytes). The analytes were stable in serum for at least 10 months when stored at -20 degrees C. Intra- and inter-day accuracy were in the range 91-107 and 93-103%, respectively. In clinical samples (n = 14, median mirtazapine dose 45 mg per day, range 15-45 mg per day) the median (range) mirtazapine and normirtazapine concentrations were 26 (8-40) and 21 (8-32) microg/l, respectively.
Morgan
P E
PE
Medical Toxicology Unit, Guy's and St. Thomas' Hospital Trust, London SE14 5ER, UK. phillip.morgan@gstt.nhs.uk
Tapper
J
J
Spencer
E P
EP
D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008803:Mianserin / Q000031:analogs & derivatives* / Q000097:blood*; D000078785:Mirtazapine; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence / Q000379:methods*
D008803:Mianserin; D000078785:Mirtazapine