US EPA

1447621 

Journal Article 

A simple and reliable method for quantifying plasma concentrations of tetracyclic antidepressants using monolithic silica solid-phase extraction tips 

Hayashi, D; Kumazawa, T; Hasegawa, C; Lee, XPen; Marumo, A; Uchigasaki, S; Kawamura, M; Sato, K 

2012 

Yes 

Forensic Toxicology
ISSN: 1860-8965
EISSN: 1860-8973 

30 

2 

98-105 

10.1007/s11419-012-0132-y 

WOS:000306427300002 

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 C-18. The plasma
samples (0.1 ml), which contained mianserin, mirtazapine, and setiptiline, were mixed with 330 mu
l of distilled water and 50 mu l of 0.5 M glycine-sodium hydroxide buffer solution (pH 8). After
centrifugation, the supernatant was extracted onto the C-18 phase of the tip (pipette tip volume,
200 mu l) by 25 sequential aspirating/dispensing cycles. The three analytes retained in the C-18
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 4A degrees C, 4 weeks at -80A
degrees 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. 

Tetracyclic antidepressants; Monolithic silica solid-phase extraction; Pipette tip; Mianserin; Mirtazapine; Setiptiline