Abstract
A rapid and reliable UPLC-MS/MS method was developed and validated for the simultaneous quantification of thirteen bioactive compounds (luteolin, cynaroside, luteolin 7-O-glucuronide, isochlorogenic acid C, chlorogenic acid, cryptochlorogenic acid, apigenin, apigenin 7-glucoside, acacetin, hyperoside, isoquercitrin, tilianin, and hesperidin) in rat plasma. The compounds were separated on an ACQUITY UPLC BEH C18 column (2.1 × 100 mm, 1.7 μm) with a gradient mobile phase system of acetonitrile and 0.1% (v/v) formic acid aqueous solution at a flow rate of 0.3 mL/min. All compounds were quantitated using Agilent Jet Stream electrospray ionization (AJS ESI) in a negative ion mode. The lower limit of quantification (LLOQ) for all compounds was below 5 ng/mL. The intra- and interday accuracy ranged from -13.0% to 14.0%, and precisions were less than 12.2%. The extraction recoveries of the compounds were in the range of 56.9% to 95.0%, and the matrix effect ranged between 71.6% and 109.3%. Stability studies proved that the thirteen compounds were stable under tested conditions, with a relative standard deviation (RSD) of less than 11.4%. This developed method was successfully applied to the pharmacokinetic study of the 13 bioactive compounds after oral administration of Flos Chrysanthemi extract in rat by UPLC-MS/MS. Pharmacokinetic parameters of 8 out of the 13 compounds investigated are presented in this paper.
Highlights
Flos Chrysanthemi is a dried capitulum belonging to the Compositae family and is native to Asia and northeastern Europe [1,2,3]
Plasma samples acquired at 0.08 h after oral administration of Flos Chrysanthemi extract were compared to spiked plasma samples and blank plasma samples from six different rats to evaluate method specificity and identify endogenous interfering substances
Both positive and negative ion modes of the Agilent Jet Stream electrospray ionization (AJS ESI) source were experimented for optimal mass spectrometry results
Summary
Flos Chrysanthemi is a dried capitulum belonging to the Compositae family and is native to Asia and northeastern Europe [1,2,3]. There are 7 different varieties of Flos Chrysanthemi, namely, Haoju, Chuju, Gongju, Hangju (Dabaiju, Huju, and Xiaobaiju), and Huaiju [4]. Various studies have identified three different types of bioactive compounds in Flos Chrysanthemi, namely, flavonoids, caffeic acid, and phenolics, which provide a series of pharmacological actions such as antioxidative activity, antiinflammatory activity, anticancer activity, lipid-lowering effect in a fatty liver, and antiangiogenic activity [6,7,8,9,10,11,12,13]. There are a few pharmacokinetic studies on luteolin, apigenin, diosmetin, and chrysoeriol in oral Flos Chrysanthemi extract [14,15,16]. The pharmacokinetics of Flos Chrysanthemi has not been comprehensively evaluated in the existing studies because its extract contains a wide variety of chemical compounds. It is of relevance to further research the pharmacokinetics of various ingredients in rat plasma after the oral intake of Flos Chrysanthemi extract
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