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. 2018 Dec 25;24(1):64.
doi: 10.3390/molecules24010064.

Simultaneous Determination of Five Phenolic Acids and Four Flavonoid Glycosides in Rat Plasma Using HPLC-MS/MS and Its Application to a Pharmacokinetic Study after a Single Intravenous Administration of Kudiezi Injection

Peiying Shi  1 , Chunlei Yang  2 , Ya Su  3 , Liying Huang  4 , Xinhua Lin  5 , Hong Yao  6
Affiliations

Simultaneous Determination of Five Phenolic Acids and Four Flavonoid Glycosides in Rat Plasma Using HPLC-MS/MS and Its Application to a Pharmacokinetic Study after a Single Intravenous Administration of Kudiezi Injection

Peiying Shi et al. Molecules. .

Abstract

This study has developed a reliable and precise high performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of five phenolic acids and four flavonoid glycosides in rat plasma after a single intravenous administration of Kudiezi injection (KI). Chromatographic separation was carried out on an Ultimate®XB-C18 column (4.6 × 100 mm, 3.5 μm) using a gradient elution program with a mobile phase consisting of water containing 0.5% acetic acid and acetonitrile at a flow rate of 0.6 mL/min. Detection was performed on a triple-quadrupole tandem mass spectrometry using multiple reaction monitoring in negative electrospray ionization mode. The calibration curves of all analytes showed good linearity (R² > 0.990). The results of selectivity, intra-day and inter-day precisions, extraction recoveries, matrix effects and stability were satisfactory. Pharmacokinetic parameters showed that luteolin-7-O-β-d-gentiobioside, luteolin-7-O-β-d-glucuronide, luteolin-7-O-β-d-glucoside and apigenin-7-O-β-d-glucuronide were eliminated quickly (0.07 h < t1/2 < 0.66 h), whereas 5-caffeoylquinic acid, caftaric acid, chlorogenic acid, 4-caffeoylquinic acid and caffeic acid were eliminated relatively slowly (2.22 h < t1/2 < 6.09 h) in rat blood. The pharmacokinetic results would be valuable to identify bioactive constituents, elucidate mechanisms of pharmacological actions or adverse drug reactions and guide the rational clinical use of KI.

Keywords: Kudiezi injection; flavonoid glycosides; high performance liquid chromatography-tandem mass spectrometry; pharmacokinetics; phenolic acids.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structures of the nine compounds.
Figure 2
Figure 2
The multiple reaction monitoring (MRM) chromatograms of nine compounds and internal standard (IS) in negative mode. a, I; b, II; c, III; d, IV; e, V; f, VI; g, VII; h, VIII; i, IX and j, IS.
Figure 2
Figure 2
The multiple reaction monitoring (MRM) chromatograms of nine compounds and internal standard (IS) in negative mode. a, I; b, II; c, III; d, IV; e, V; f, VI; g, VII; h, VIII; i, IX and j, IS.
Figure 2
Figure 2
The multiple reaction monitoring (MRM) chromatograms of nine compounds and internal standard (IS) in negative mode. a, I; b, II; c, III; d, IV; e, V; f, VI; g, VII; h, VIII; i, IX and j, IS.
Figure 3
Figure 3
The mean drug plasma concentration-time curves of nine compounds after intravenous administration of 3.6 mL/kg of concentrated KI.
Figure 3
Figure 3
The mean drug plasma concentration-time curves of nine compounds after intravenous administration of 3.6 mL/kg of concentrated KI.
See this image and copyright information in PMC

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