Quantitative determination of a novel enantiomeric tropane analog, (−)‐satropane,in biological fluids using liquid chromatography/tandem mass spectrometry

A sensitive, accurate and precise liquid chromatography–tandem mass spectrometry method was developed for the determination of (?)‐satropane (3α‐paramethyl‐benzenesulfonyloxy‐6β‐acetoxy‐tropane) in rabbit aqueous humor. Since (?)‐satropane may be absorbed from the aqueous humour with resultant systemic side effects, the LC‐MS/MS method was also evaluated for its applicability in analyzing plasma samples containing this compound. (?)‐Satropane and phentolamine (the internal standard, represented as IS) were detected by multiple reaction monitoring using the transitions m/z 354–182 and 282–212, respectively. The calibration curve was linear over the ranges 2–500 and 5–1000 ng/mL, and the values of the lower limit of quantification were 2 and 5 ng/mL for the microdialysis dialysate and rat plasma samples, respectively. The intra‐day and inter‐day precision and accuracy were better than 8.6 and 6.00%, respectively, in both matrices investigated. The absolute recovery of the plasma samples was more than 76.30%. The average matrix effects of (?)‐satropane were 91.72 and 83.05% in the microdialysis dialysate and plasma samples, respectively. The validated method was successfully applied to analyze (?)‐satropane in microdialysis dialysate and rat plasma samples, and this assay has been used to quantify (‐)‐satropane in the pharmacokinetic and toxicokinetic studies in our laboratory. Copyright © 2009 John Wiley & Sons, Ltd.