title: Sensitive and robust UPLC-MS/MS method to determine the gender-dependent pharmacokinetics in rats of emodin and its glucuronide.
abstract: In this study, a sensitive and robust ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed, validated, and applied to determine gender-dependent pharmacokinetics of total emodin (aglycone+glucuronide) in male and female Sprague-Dawley rats. The lower limit of quantification for emodin and emodin glucuronide in rat plasma was 39 and 78 ng/ml, with signal-to-noise ratio of ≥ 10. Precision and accuracy studies showed emodin and emodin glucuronide plasma concentrations well within the 10% range in all studies. Plasma recovery of emodin and emodin glucuronide was always above 86% for low (emodin: 39 ng/ml; glucuronide: 78 ng/ml), 92% for medium (625 ng/ml), and 97% for high (10000 ng/ml) concentrations. Furthermore, emodin showed more than 95% plasma stability under short-term and long-term storage conditions, as well as after three freeze-thaw cycles in the experiments. The developed and validated analytical method was successfully applied to study the gender-dependent 10-fold higher oral bioavailability of total emodin in male than female rats. The oral bioavailability of emodin and emodin glucuronide was also measured separately and showed a statistically significant gender difference in oral bioavailability of emodin and emodin glucuronide in rats.
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Zheng
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.forename: Ling
authors.initials: L
authors.lastname: Ye
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.forename: Ming
authors.initials: M
authors.lastname: Hu
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002853:Chromatography, Liquid / Q000295:instrumentation / Q000379:methods*; D004642:Emodin / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D020719:Glucuronides / Q000097:blood*; D007275:Injections, Intravenous; D057230:Limit of Detection; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012727:Sex Characteristics; D053719:Tandem Mass Spectrometry / Q000295:instrumentation / Q000379:methods*
chemical_list: D020719:Glucuronides; D004642:Emodin