Characterization of multiple constituents in Kai-Xin-San prescription and rat plasma after oral administration by liquid chromatography with quadrupole time-of-flight tandem mass spectrometry

Abstract

A sensitive and reliable ultra high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry method was established to separate and identify the chemical constituents of Kai-Xin-San prescription, a classic traditional Chinese medicine formula that plays an important role in the treatment of Alzheimer's disease. The detection was performed on an Agilent 6520 Accurate-Mass quadrupole time-of-flight mass spectrometer equipped with an electrospray ionization source in negative modes. With the optimized conditions, a total of 54 compounds were identified or tentatively characterized. Out of the 54 compounds, six compounds were identified by comparing the retention time and mass spectrometry data with reference standards, the rest were characterized by analyzing mass spectrometry data and retrieving the literature data. Results indicated ginsenosides, polygala saponins, terpenoids, and oligosaccharide esters were the major effective constituents in Kai-Xin-San prescription. There were 26 prototype ingredients that were assigned for identification in rat plasma. It is also concluded that the developed ultra high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry method with high sensitivity and resolution is suitable for identifying and characterizing the chemical constituents of Kai-Xin-San prescription, and the analysis provides a helpful chemical basis for further research on Kai-Xin-San prescription and the clinical diagnostics of Alzheimer's disease.

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

“…In addition, the compounds mentioned above, including POL, SB, Te, A5, A6, TenA, GRe and GRb1 (Fig. ) were found to possess good absorption in vivo according to previous research .…”

Identification and determination of the major constituents in Kai‐Xin‐San by UPLC‐Q/TOF MS and UFLC‐MS/MS method

“…About the 92 compounds, there were 53 from Radix Polygalae, 36 from Ginseng Radixet Rhizoma, and 3 from Poria. Including 24 compounds were unambiguously identified by comparing the retention time and MS peaks with the reference standards; the other 68 compounds were identified using MassHunter Data Acquisition Workstation software to carefully study their MS spectra, MS/MS spectra and comparing with the literature data . Generally, a mass error below 5 ppm is regarded as acceptable certainty.…”

“…Including 24 compounds were unambiguously identified by comparing the retention time and MS peaks with the reference standards; the other 68 compounds were identified using MassHunter Data Acquisition Workstation software to carefully study their MS spectra, MS/MS spectra and comparing with the literature data. [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] Generally, a mass error below 5 ppm is regarded as acceptable certainty. The MS data of the compounds are listed in Table 2, and their chemical structures are shown in the Supporting Information.…”

“…Furthermore, there have been few reports about the absorption and metabolism of the active compounds in vivo . We recently reported a method to investigate the chemical constituents in KXS, but there are sparse data for comprehensive investigation on the constituents of KXS and lack of omnibearing quality control.…”

Comprehensive Qualitative Ingredient Profiling of Chinese Herbal Formula Wu-Zhu-Yu Decoction via a Mass Defect and Fragment Filtering Approach Using High Resolution Mass Spectrometry

“…In addition, comparing with other high resolution MS like Orbitrap and FT-ICR, a much higher acquisition rate up to 100 spectra/s is the most remarkable characteristics of a QTOF mass spectrometer and may lead the exploration of complex samples to greater depth [9,10,11]. These characteristics of comprehensive qualitative exploration and rapid profiling of target and unknown compounds make the QTOF MS system extraordinarily suitable for qualitative analysis of a complex herbal extract [12,13,14]. In previous reports, detection of the TCM components from full scan mass chromatograms using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF MS) used to be performed manually with low efficiency.…”