Ultra-fast liquid chromatography with tandem mass spectrometry determination of eight bioactive components of Kai-Xin-San in rat plasma and its application to a comparative pharmacokinetic study in normal and Alzheimer's disease rats

Abstract

A method of ultra-fast liquid chromatography with tandem mass spectrometry was developed and validated for the simultaneous quantitation of eight bioactive components, including polygalaxanthone III, sibiricaxanthone B, tenuifolin, sibiricose A5, sibiricose A6, tenuifoliside A, ginsenoside Re and ginsenoside Rb1 in rat plasma after oral administration of Kai-Xin-San. The plasma samples were extracted by liquid-liquid extraction using digoxin as an internal standard. Chromatographic separation was performed on a Venusil MP C column (100 mm × 2.1 mm, 3 μm) with methanol and 0.05% acetic acid in water as mobile phase. The tandem mass spectrometric detection was performed in the multiple reaction monitoring with turbo ion spray source in the negative ionization. Validation parameters were within acceptable ranges. The established method has been successfully applied to compare the pharmacokinetic profiles of the analytes between normal and Alzheimer's disease rats. The results indicated that there were significant differences in pharmacokinetic parameters of some components between two groups, which may be due to the mechanisms of Alzheimer's disease and pharmacological effects of the analytes. The pharmacokinetic research in the pathological state might provide more useful information to guide the clinical usage of herbal medicine.

Study on the Multitarget Synergistic Effects of Kai-Xin-San against Alzheimer’s Disease Based on Systems Biology

“…Briefly, the AD rats were injected intraperitoneally with D-gal (50 mg/kg/mL) for 6 weeks and the control group was given the same volume of saline. Six groups of AD rats were administered intragastrically with KXS (10.0 g/kg), GR (3.0 g/kg), PR (2.0 g/kg), PO (3.0 g/kg), AT (2.0 g/kg), and Hup A (0.027 mg/kg) once a day from the third week until the end of the experiment [25]. At the end of the fourth week, the stereotaxic injection of 4 μg Aβ [25][26][27][28][29][30][31][32][33][34][35] (1 μg/μL) was operated at the following coordinates: anteroposterior-3.5; mediolateral-+2.0; and dorsoventral-2.8 mm [26].…”

Classic Prescription, Kai-Xin-San, Ameliorates Alzheimer’s Disease as an Effective Multitarget Treatment: From Neurotransmitter to Protein Signaling Pathway

“…Briefly, AD rats were injected with D-gal (50 mg/kg/d) intraperitoneally for 6 weeks, and control rats were given the same volume of saline. KXS (10 g/kg/d) and Hup A (30 μ g/kg/d) were oral administrated from the third week until the end of the experiment once a day [10]. The stereotaxic injection of 4 μ g A β 25-35 (1 μ g/ μ L) was operated as described previously [11].…”

Influence Factors of the Pharmacokinetics of Herbal Resourced Compounds in Clinical Practice

“…For the past few years, many researches have focused on this issue. They found that pathological factors such as liver injury, diabetes, stroke, fever, rheumatoid arthritis, migraine, coronary atherosclerotic heart disease, cancer, and neurodegenerative diseases demonstrate deep impact on metabolism of HRC [8, 67–75]. Hepatocytes are the parenchymal cells of liver which can improve the excretion of xenobiotics through urine or feces by modifying their structure, including phase I xenobiotic metabolism like oxidation or hydrolysis, followed by phase II metabolism like glucuronidation, sulfation, acetylation, or glutathione conjugation.…”