Determination of mianserin and metabolites in plasma by liquid chromatography with electrochemical detection

A procedure for the determination of mianserin, desmethylmianserin, and 8-hydroxymianserin in plasma at therapeutic concentrations by liquid chromatography with electrochemical detection is described. Following a multiple-step extraction from alkaline plasma into methyl-tert-butyl ether, the reconstituted extract was injected onto a reversed-phase trimethylsilyl-packed column and eluted with an acetate-acetonitrile mobile phase containing an ion-paired reagent. The method provides an absolute recovery of 71-76% and a day-to-day precision of 5.4-9.1% for each compound at 25 ng/ml. The minimum quantifiable level for all three compounds was 5 ng/ml (RSD greater than 11%), and the detector response was linear up to 500 ng/ml. Fixed-dose steady-state plasma level data for 34 patients are reported.