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.
Highlights
Kudiezi injection (KI) is a traditional Chinese medicine (TCM) injection made from Ixeris sonchifolia (Bunge) and its major components are phenolic acids, flavonoids, nucleosides and sesquiterpene lactones [1,2,3]
Results and Discussion bioanalysis, method validation was performed referring to selectivity, For bioanalysis, aaa method method validation validation was was performed performed referring referring to to selectivity, selectivity, For the the liquid chromatography-mass spectrometry (LC-MS)/MS
Previous studies have reported that the composition of TCMs are complex, and the pharmacological actions of TCMs are thought to result from the synergistic effects of multiple ingredients [24,25]
Summary
Kudiezi injection (KI) is a traditional Chinese medicine (TCM) injection made from Ixeris sonchifolia (Bunge) and its major components are phenolic acids, flavonoids, nucleosides and sesquiterpene lactones [1,2,3]. KI has the pharmacological effects of anti-acute myocardial ischemia [4,5], anti-cerebral ischemia [6,7], anti-hyperlipidemia [8] and so on. Adverse reactions of KI have been reported. Molecules 2019, 24, 64 anaphylactic shock, palpitation, vomiting, chill, skin itch and rash, and the analysis results of the influence factors showed that the occurrence of the adverse drug reaction (ADR) could be related to the maximum blood plasma concentration of, the duration of medication in the blood circulation and the dosage of the drug [13]. Understanding the in vivo pharmacokinetic and disposition properties of KI components and formulating the rational dosage regimens are very important
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