Quantitative determination of SC-68328 in dog plasma using flow injection and tandem mass spectrometry.
A flow injection/tandem mass spectrometric assay was developed to quantitate SC-68328 in dog plasma using its stable isotopic analog [13C4]SC-68328 as an internal standard (IS). Since SC-68328, a manganese-based superoxide dismutase mimetic, is very unstable, very polar and adheres to silica-based high-performance liquid chromatographic columns, the analyte and IS were derivatized to their bis-isothiocyanate forms followed by a liquid-liquid extraction with methylene chloride and analyzed using positive ion electrospray mass spectrometric detection. SC-68328 was quantitated using the peak-height ratio of SC-68328 to its IS using MS/MS in the multiple reaction monitoring mode. The lower limit of quantitation of the assay was 0.25 microg ml(-1) SC-68328 in dog plasma with an inter-day precision of 11.8% and an accuracy of 113% (n = 12). Acceptable precision and accuracy were also obtained for concentrations in the calibration curve range (0.25-10 microg ml(-1) SC-68328 in dog plasma).
Zhang
J Y
JY
Metabolism and Safety Evaluation, Searle R&D, Skokie, Illinois 60077, USA. ji.y.zhang@monsanto.com
Fast
D M
DM
Schoenhard
G L
GL
Arora
V K
VK
Belas
F J
FJ
Blair
I A
IA
D000818:Animals; D001774:Blood Chemical Analysis / Q000379:methods* / Q000592:standards / Q000706:statistics & numerical data; D004285:Dogs; D013058:Mass Spectrometry / Q000379:methods* / Q000592:standards / Q000706:statistics & numerical data; D009942:Organometallic Compounds / Q000097:blood* / Q000737:chemistry / Q000494:pharmacology; D011786:Quality Control; D013482:Superoxide Dismutase / Q000494:pharmacology
D009942:Organometallic Compounds; C408296:SC 68328; D013482:Superoxide Dismutase