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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-C 18 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 &gt; 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 &lt; t  1/2 &lt; 0.66 h), whereas 5-caffeoylquinic acid, caftaric acid, chlorogenic acid, 4-caffeoylquinic acid and caffeic acid were eliminated relatively slowly (2.22 h &lt; t  1/2 &lt; 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.

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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