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Three tetracyclic antidepressants, mianserin, mirtazapine, and setiptiline, were extracted from human plasma samples using a new micropipette solid-phase extraction tip containing a monolithic silica gel packing material, the MonoTip C18. The plasma samples (0.1 ml), which contained mianserin, mirtazapine, and setiptiline, were mixed with 330 μl of distilled water and 50 μl of 0.5 M glycine–sodium hydroxide buffer solution (pH 8). After centrifugation, the supernatant was extracted onto the C18 phase of the tip (pipette tip volume, 200 μl) by 25 sequential aspirating/dispensing cycles. The three analytes retained in the C18 phase were eluted with methanol by 5 aspirating/dispensing cycles. The eluate was subjected to measurements by gas chromatography (GC) with nitrogen–phosphorus detection (NPD). The recoveries of the three antidepressants were 84.6–99.6% and the limits of detection for each drug were between 2.4 and 15 ng/ml of plasma. The maximum intraday and interday coefficients of variation for the drugs was below 10.6%. Regression equations for the three drugs showed excellent linearity in the range of 50–5000 ng/ml for mianserin and mirtazapine and 50–10 000 ng/ml for setiptiline. The antidepressants were stable for at least 12 h at 4°C, 4 weeks at −80°C, and through three freeze–thaw cycles in plasma. The validated method was successfully used to quantify the plasma concentrations of mirtazapine in a human subject after oral administration of the drug. Although we achieved analyte detection with GC-NPD, the present monolithic micropipette extraction method for tetracyclic antidepressants seems to be very useful for combining it with GC–mass spectrometry (MS) and/or liquid chromatography–tandem MS to secure high simplicity, purification, reproducibility, and sensitivity.

A simultaneous determination of 20 antidepressant drugs (imipramine, amitriptyline, desipramine, trimipramine, nortriptyline, clomipramine, amoxapine, lofepramine, dosulepin, maprotiline, mianserin, setiptiline, trazodone, fluvoxamine, paroxetine, milnacipran, sulpiride, tandspirone, methylphenidate and melitracen) in human plasma was developed using LC/MS with sonic spray ionization (SSI) method. These drugs showed good separation and sensitivity by LC–MS using an Inertsil C-8 column with methanol:10 mM ammonium acetate (pH 5.0):acetonitrile (70:20:10) as mobile phase at 0.10 mL/min at 35 °C. Solid-phase extraction of these drugs added to the human plasma was performed with an Oasis ® HLB cartridge column. Recovery and limit of detection of these drugs were between 69 and 102% and between 0.03 and 0.63 μg/mL, respectively. The present procedure offers an easier and more convenient screening method for antidepressants, and will be useful for forensic toxicology investigations.

Tetracyclic antidepressants, mianserin and setiptiline, in human body fluids have been found measurable with high sensitivity by gas chromatography (GC) with surface ionization detection (SID). The compounds in human whole blood or urine samples were extracted by solid-phase extraction using Bond Elut C 18 cartridges. The recoveries of both compounds from the body fluids were above 85%. For quantitation of mianserin, 25 ng of setiptiline was used as internal standard; and for quantitation of setiptiline, vice versa . The calibration curves for spiked whole blood or urine samples were linear in the range of 1.25–50 ng/ml. The detection limit of mianserin and setiptiline was about 1 ng/ml, which is comparable to those obtained by the previous GC-mass spectrometry methods. Our method seems very useful for determination of mianserin and setiptiline in forensic and clinical toxicology, because of high sensitivity, low background impurities and easy handling of the GC instrument.

A simple and sensitive method for analysis of three tetracyclic antidepressants, maprotiline, mianserin, and setiptiline, in human whole blood was developed using headspace-solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS). A vial containing a blood sample, sodium hydroxide, and imipramine as an internal standard was heated at 120 degrees C. The extraction fiber of the SPME was exposed for 45 min in the headspace of the vial. The compounds absorbed on the fiber were desorbed by exposing the fiber in the injection port of a GC-MS. The calibration curves, using an internal standard method, demonstrated good linearity throughout the concentration range from 0.005 to 5.0 microg/g for mianserin and setiptiline and from 0.025 to 25 microg/g for maprotiline. No interferences were found, and the time for analysis was 60 min for one sample. In addition, this proposed method was applied to a medicolegal case in which the cause of death was suspected to be acute setiptiline poisoning. Setiptiline was detected in the left and right heart blood samples of the victim at concentrations of 1.77 and 0.78 microg/g, respectively.

1. 1. Setiptiline maleate (SPT) was administered orally to 45 subjects aged 22–86 years and steady state plasma levels were determined by mass fragment chromatography (GC-MF) to examine the effect of aging on those values. 2. 2. There was a significant correlation between the plasma levels and daily dose. However, there was a wide interindividual variability. 3. 3. Dose-corrected plasma level (DC-PL), or values corrected by dividing the plasma level by daily dose/body weight, was used as the systemic drug clearance parameter. 4. 4. DC-PL was compared among 7 age groups of the subjects distributed in 10-year-intavals. DC-PL showed no difference among groups of subjects between the > 29 years bracket to the 70 years bracket, but showed significantly higher values in those in the > 80 bracket compared to all age groups and subjects in the < 79 bracket. 5. 5. There was a significant correlation between the age of patients and DC-PL according to polynomial response curve analysis. Regression analysis yielded te equation y = −52.72 + 7.05 × −0.17 x2 + 0.01 x3 (n = 45, r = 0.49, p