Liquid chromatography-electrospray tandem mass spectrometric assay suitable for quantitation of YM155, a novel small-molecule survivin suppressant, in dog plasma.
This paper describes a sensitive and selective liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for determination of the novel survivin suppressant YM155, 1-(2-methoxyethyl)-2-methyl-4,9-dioxo-3-(pyrazin-2-ylmethyl)-4,9-dihydro-1H-naphtho[2,3-d]imidazolium, which is developed for the treatment of solid tumors. This method uses a liquid-liquid extraction from 0.25 mL of dog plasma. LC separation was carried out on a Genesis Silica column (50 mm x 3.0 mm i.d.) at a flow-rate of 0.5 mL/min. Compounds were eluted using a mobile phase of 5 mm ammonium acetate and 0.1% formic acid in water-0.1% formic acid in acetonitrile, 17:83 (v/v). MS/MS detection was carried out with an MDS-Sciex API3000 triple quadrupole mass spectrometer in positive electrospray ionization mode. The standard curve was linear from 0.05 to 50 ng/mL (r > or = 0.9968). The lower limit of quantitation was 0.05 ng/mL. Good intra- and inter-day assay precision (within 7.4% RSD) and accuracy (within +/-12.3%) were obtained. The extraction recovery was 66.2%. The method was successfully applied to preclinical pharmacokinetic studies in dogs.
Minematsu
Tsuyoshi
T
Drug Metabolism Research Laboratories, Astellas Pharma Inc., 1-1-8 Azusawa, Itabashi-ku, Tokyo 174-8511, Japan. tsuyoshi.minematsu@jp.astellas.com
Felder
Laurie
L
Oppeneer
Todd
T
Sakazume
Masashi
M
Oikawa
Keishi
K
Hashimoto
Tadashi
T
Usui
Takashi
T
Kamimura
Hidetaka
H
D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D004285:Dogs; D007093:Imidazoles / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D016014:Linear Models; D009285:Naphthoquinones / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
D007093:Imidazoles; D009285:Naphthoquinones; C523798:sepantronium