Simultaneous determination of flavonol glycoside and its major metabolites by LC-MS/MS in rat plasma
10.16438/j.0513-4870.2018-0086
- VernacularTitle:LC-MS/MS法测定大鼠血浆中黄酮醇糖苷及其主要代谢物
- Author:
Lei DONG
1
;
Jin-qiu LIU
2
;
Liang LI
2
;
Xiao-yan CHEN
2
;
Wei-guang SHAN
1
;
Da-fang ZHONG
1
Author Information
1. College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China
2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
LC-MS/MS;
flavonol glycoside;
glucuronide conjugate;
pharmacokinetics
- From:
Acta Pharmaceutica Sinica
2018;53(8):1344-1350
- CountryChina
- Language:Chinese
-
Abstract:
Flavonol glycoside is in clinical trials for treatment of hyperlipidemia. An accurate and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of flavonol glycoside (M0), aglycone (M1) and glucuronide conjugate (M2) in rat plasma. d6-Flavonol glycoside was used as internal standard (IS). After extraction from the plasma by protein precipitation, the analytes and internal standard were separated on a XDB C18 column (50 mm×4.6 mm, 1.8 μm) using a gradient elution procedure. The mobile phase consisted of methanol and water (0.2% formic acid) at a flow rate of 0.6 mL·min−1. The total run time was 4.5 min. Positive electrospray ionization was performed using multiple reaction monitoring (MRM) with transitions of m/z 461.3 → m/z 299.1 for M0, m/z 299.1 → m/z 283.1 for M1, m/z 475.0 → m/z 299.1 for M2, and m/z 467.3 → m/z 305.1 for d6-flavonol glycoside. The method was validated and successfully applied to the pharmacokinetics study of flavonol glycoside in SD rats which were given flavonol glycoside (30 mg·kg−1) by gavage. The Cmaxof M0 is (341 ±106) ng·mL−1 and AUC0−t is (1 960 ±725) h·ng·mL−1, while the Cmaxof M2 is (1 720 ±843) ng·mL−1and AUC0−t is (8 510 ±2 920) h·ng·mL−1. The results suggest that flavonol glycoside existed mainly in the form of M0 and M2 in rats. After flavonol glycoside being hydrolyzed by the intestinal flora, it was absorbed in the form of aglycone and further metabolized to M2 after the first-pass effect. In this paper, the main metabolites of flavonol glycoside in rat plasma were determined for the first time, which provided a basis for the design of clinical pharmacokinetic experiment.
