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A simple LC–MS/MS method facilitated by salting‐out assisted liquid–liquid extraction to simultaneously determine trans ‐resveratrol and its glucuronide and sulfate conjugates in rat plasma and its application to pharmacokinetic assay
Author(s) -
Qiu Zhixia,
Yu Jiaojiao,
Dai Yu,
Yang Yue,
Lu Xiaoyu,
Xu Jiaqiu,
Qin Zhiying,
Huang Fang,
Li Ning
Publication year - 2017
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.4001
Subject(s) - chemistry , chromatography , glucuronide , metabolite , extraction (chemistry) , solid phase extraction , analyte , protein precipitation , sample preparation , bioavailability , salting out , liquid–liquid extraction , pharmacokinetics , aqueous solution , pharmacology , biochemistry , medicine
A simple LC–MS/MS method facilitated by salting‐out assisted liquid–liquid extraction (SALLE) was applied to simultaneously investigate the pharmacokinetics of trans‐ resveratrol (Res) and its major glucuronide and sulfate conjugates in rat plasma. Acetonitrile–methanol (80:20, v /v) and ammonium acetate (10 mol L −1 ) were used as extractant and salting‐out reagent to locate the target analytes in the supernatant after the aqueous and organic phase stratification, then the analytes were determined via gradient elution by LC–MS/MS in negative mode in a single run. The analytical method was validated with good selectivity, acceptable accuracy (>85%) and low variation of precision (<15%). SALLE showed better extraction efficiency of target glucuronide and sulfate conjugates (>80%). The method was successfully applied to determine Res and its four conjugated metabolites in rat after Res administration (intragastric, 50 mg kg −1 ; intravenous, 10 mg kg −1 ). The systemic exposures to Res conjugates were much higher than those to Res (AUC 0– t , i.v., 7.43 μ m h; p.o., 8.31 μ m h); Res‐3‐ O‐β ‐ d ‐glucuronide was the major metabolite (AUC 0– t , i.v., 66.1 μ m h; p.o., 333.4 μ m h). The bioavailability of Res was estimated to be ~22.4%. The reproducible SALLE method simplified the sample preparation, drastically improved the accuracy of the concomitant assay and gave full consideration of extraction recovery to each target analyte in bio‐samples.