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The aim of this research was to find out whether increased plasma cortisol levels appear in unipolar or bipolar patients with major depressive disorder (MDD) and whether the effective antidepressant treatment by imipramine and fluoxetine leads to regulation of the cortisol level. Cortisol levels were studied in two groups of patients with major depressive disorder: unipolar and bipolar patients treated with fluoxetine (doses: 20-60 mg/day). This group included 5 patients (age 29-46 yr); unipolar and bipolar subjects treated with imipramine (50-150 mg/day), this group included 5 patients (aged 24-70 yr). Cortisol and fluoxetine or imipramine plasma levels were assessed using HPLC methods: before treatment, after 3, 6 and 24 h of drug administration as well as in the 2nd, 4th, 6th, and 8th week of antidepressant treatment. HPLC methods were previously validated. The research conducted and the clinical data may be useful for proving the essential role of enhanced HPA axis activity for the pathogenesis and depressive disorder proceedings.

A high performance liquid chromatography method for the determination of mianserin in human serum was developed and validated. Doxepin was used as an internal standard. Mianserin was extracted from human serum using a liquid-liquid extraction with hexane:isoamyl alcohol (99:1, v/v). The sample was then dissolved in 0.05 M phosphoric acid (pH=3.0), and after separation on a Hichrom RPB (250 x 4.6 mm, 5 mm) column, the analytes were measured by ultraviolet detection at 214 nm. The recovery ranged from 86.1 to 94.5% for mianserin. The method was specific and linear over the concentration range of 2.0-128.0 ng/mL. The limit of quantification (LOQ) was established at 2.0 ng/mL (CV=13.8%). The accuracy range was from 92.5 to 107.5%. The method was used to measure mianserin in human serum samples obtained from healthy volunteers who had received a single oral dose of 30 mg mianserin. Pharmacokinetic parameters obtained for the mianserin were in agreement with the existing data.