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 (3alpha-paramethyl-benzenesulfonyloxy-6beta-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.
Fu
Jun
J
Institute of Drug Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
Fang
Chao
C
Cui
Yong-Yao
YY
Yang
Li-Min
LM
Zhu
Liang
L
Feng
Xue-Mei
XM
Zheng
Pei-Li
PL
Lu
Yang
Y
Chen
Hong-Zhuan
HZ
D000818:Animals; D001082:Aqueous Humor / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D005901:Glaucoma / Q000378:metabolism; D016014:Linear Models; D017551:Microdialysis; D011817:Rabbits; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014326:Tropanes / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics
D014326:Tropanes; C535253:satropane