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 µg 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 µg ml−1 SC‐68328 in dog plasma). Copyright © 2000 John Wiley & Sons, Ltd.