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 (3 α ‐paramethyl‐benzenesulfonyloxy‐6 β ‐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.