Ultrasensitive determination of NE-100, a novel sigma ligand, in human plasma by liquid chromatography and electrospray ionization tandem mass spectrometry combined with a column-switching technique.
For the highly sensitive and selective determination of NE-100, a novel sigma ligand, at levels of low picogram per milliliter of human plasma, a method with excellent reliability employing liquid chromatography (LC)-electrospray ionization (ESI) tandem mass spectrometry (MS-MS) combined with a column-switching technique has been developed. The method involves the use of a stable isotope labeled compound as the internal standard (I.S.), liquid-solid extraction of a plasma specimen with a C8 cartridge, automated on-line clean-up on a short trapping column, subsequent separation on a micro-bore C18 column and detection with ESI-MS-MS using m/z 356 ([M+H]+) as a precursor ion and m/z 105 as a product ion in a selected reaction monitoring mode. The detection and the quantification limits of NE-100 in plasma were 0.5 pg/ml with a signal-to-noise ratio (S/N) of 3 and 2.3 pg/ml, respectively, with an S/N of 21. The good linearity of the calibration graph was obtained in the range of 2.3 to approximately 907.0 pg/ml with excellent reliability. The developed method was applied to the determination of NE-100 in plasma obtained from the clinical trail.
Yamaguchi
J
J
Pharmaceutical Research Laboratories, Taisho Pharmaceutical Co., Ltd., Ohmiya-shi, Saitama, Japan.
Watanabe
Y
Y
Ohmichi
M
M
Jingu
S
S
Ogawa
N
N
Kokatsu
J
J
Fukushima
K
K
Goto
J
J
D000840:Anisoles / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D014150:Antipsychotic Agents / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D011437:Propylamines / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D017480:Receptors, sigma / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000840:Anisoles; D014150:Antipsychotic Agents; D011437:Propylamines; D017480:Receptors, sigma; C083832:N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride