Xie-an Yu

Simultaneous determination of four phenolic acids and seven alkaloids in rat plasma after oral administration of traditional Chinese medicinal preparation Jinqi Jiangtang Tablet by LC-ESI–MS/MS

A rapid, sensitive and selective high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of four phenolic acids (neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid and ferulic acid) and seven alkaloids (berberine, epiberberine, coptisine, magnoflorine, berberubine, palmatine and jatrorrhizine) in rat plasma. After mixing with the internal standards tetrahydropalmatine (IS1) and rosmarinic acid (IS2), plasma samples were pretreated by protein precipitation using acetonitrile. The HPLC analysis was performed on an Agilent Eclipse plus C18 (4.6 mm×100 mm, 1.8 μm) column with mobile phase consisting of 0.1% formic acid aqueous solution and acetonitrile at a flow rate of 0.3 mL min(-1). The detection was accomplished for the analytes and internal standards using positive electrospray ionization for the alkaloids and negative electrospray ionization for the phenolic acids in multiple-reaction monitoring mode. The method showed a good linearity over a wide concentration range (r(2)>0.99). The lower limit of quantification of seven alkaloids was lower than 2 ng mL(-1) and that of four phenolic acids was less than 20 ng mL(-1). The developed method was applied to the pharmacokinetic study of 11 components after oral administration of traditional Chinese medicinal preparation Jinqi Jiangtang Tablet in rats.

A Green Antioxidant Activity-Integrated Dual-Standard Method for Rapid Evaluation of the Quality of Traditional Chinese Medicine Xuebijing Injection by On-Line DPPH-CE-DAD

Much attention has been focused on treatment of sepsis which leads to high mortality all over the world in every year. Antioxidant activity seems to play a prominent role in the treatment of sepsis exhibited by Xuebijing injection. The aim of the present research was to develop an on-line 1, 1-diphenyl-2-picrylhydrazyl- (DPPH-) capillary electrophoresis-diode array detector (on-line DPPH-CE-DAD) method for rapidly assessing antioxidant properties and efficacious material basis of antioxidant activity as a way of quality control of Xuebijing injection. Several parameters affecting the separation were investigated, including the pH and concentrations of buffer, SDS, β-CD, and organic modifier as well as voltage and cassette temperature. Compared to previous traditional method, this improved method shortened the experimental cycle and became more efficient because it was successfully applied to analyze total antioxidant activity and contents of twelve antioxidants of Xuebijing injection under the same condition. The results revealed that the on-line DPPH-CE-DAD method was a reagent-saving, rapid, feasible, and green technique for quality control of Xuebijing injection in terms of pharmacological activity and contents of active ingredients. It also offered new opportunities for the analysis of antioxidant activity of complex matrix.

Simultaneous Quantification of Gallic Acid, Bergenin, Epicatechin, Epicatechin Gallate, Isoquercitrin, and Quercetin-3-Rhamnoside in Rat Plasma by LC-MS/MS Method and Its Application to Pharmacokinetics after Oral Administration of Ardisia japonica Extract

Ardisia japonica is a well-known traditional Chinese medicinal herb used as a diuretic, for treating cough and for stopping uterine bleeding. A simple, sensitive, and reliable LC-MS/MS method was developed to determine six active compounds in rat plasma and this method was further applied to the pharmacokinetic study of these compounds after oral administration of Ardisia japonica extract. Acetonitrile was used to precipitate the protein in the plasma samples. Using acetonitrile and formic acid aqueous solution (0.05%) as the mobile phase, the separation of the six compounds and internal standards was achieved at a flow rate of 300 μL min−1 on an Eclipse plus C18 column at an elution time of 16 min. A tandem mass spectrometer having an electrospray ionization (ESI) source was used in the detection of the analytes and internal standards using multiple reactions monitoring (MRM) in the negative ionization mode. The LLOQ was 2, 2, 4, 2, 1, and 0.4 ng mL−1 for gallic acid, bergenin, epicatechin, epicatechin gallate, isoquercitrin, and quercetin-3-rhamnoside, respectively. The validated method was applied to the pharmacokinetic study of gallic acid, bergenin, and quercetin-3-rhamnoside in rat plasma after oral administration of A. japonica extract to rats.

Simultaneous determination of eight flavonoids in plasma using LC-MS/MS and application to a pharmacokinetic study after oral administration of Pollen Typhae extract to rats.

A sensitive, reliable and validated LC-MS/MS method was developed to determine the presence of eight flavonoids (catechin, typhaneoside, isorhamnetin-3-O-neohesperidoside, astragalin, isorhamnetin-3-O-β-d-glucoside, naringenin, kaempferol and isorhamnetin) in rat plasma. Puerarin was selected as the internal standard. Precipitation of the protein method with acetonitrile was used to extract these flavonoids from the rat plasma samples. The analysis was carried out on an Eclipse plus C18 column (4.6 mm×100mm, 1.8μm) when acetonitrile and formic acid aqueous solution (0.1%) was used as the mobile phase at a flow rate of 0.3mLmin-1. A tandem mass spectrometer having an electrospray ionization (ESI) source was used to detect eight flavonoids using multiple reaction monitoring (MRM) in the negative ionization mode. The LLOQs for catechin, typhaneoside, isorhamnetin-3-O-neohesperidoside, astragalin, isorhamnetin-3-O-β-d-glucoside, naringenin, kaempferol and isorhamnetin are 4, 4, 4, 0.8, 1, 0.4, 2 and 0.2ngmL-1, respectively. The precision, accuracy and recovery were all within acceptable limits and the analytes were stable in plasma for all conditions tested. The method was successfully applied to pharmacokinetic study of four flavonoids in rat plasma after administering Pollen Typhae extract orally to rats.

Simultaneous Determination of Bergapten, Imperatorin, Notopterol, and Isoimperatorin in Rat Plasma by High Performance Liquid Chromatography with Fluorescence Detection and Its Application to Pharmacokinetic and Excretion Study after Oral Administration of Notopterygium incisum Extract

A specific, sensitive, and reliable high performance liquid chromatography with fluorescence detection (HPLC-FLD) was first optimized and then used in the simultaneous quantification of bergapten, imperatorin, notopterol, and isoimperatorin in rat plasma using osthole as the internal standard. Liquid-liquid extraction with ethyl acetate was employed in treating the rat plasma samples obtained. Separation was carried out with a Hedera™ ODS column (4.6 × 250 mm, 5 μm) by gradient elution at a temperature of 40°C. Excitation and emission of the fluorescence detector were set to 300 and 490 nm, respectively. The lower limits of quantification for bergapten, imperatorin, notopterol, and isoimperatorin in rat plasma were 4, 40, 4, and 2 ng mL−1, respectively. The intraday and interday precision and accuracy for the four coumarins were within acceptable criteria. The recovery of the method was satisfactory with a range of 80.3–114%. The validated method was successfully used for the simultaneous determination of the four coumarins in Notopterygium incisum extracts and also for the pharmacokinetic and excretion study of bergapten, imperatorin, notopterol, and isoimperatorin in rats.

The pharmacokinetics, bioavailability and excretion of columbianetin acetate and its metabolite columbianetin were analysed in rat plasma by LC-MS/MS after administration of columbianetin acetate and Angelicae pubescentis radix extract

Angelicae pubescentis radix (APR) has been widely used in the clinic for the treatment of rheumatoid arthritis. Columbianetin acetate and its metabolite columbianetin have various biological activities. A sensitive, accurate and precise HPLC-MS/MS method was established for simultaneous determination of columbianetin acetate and columbianetin in rat plasma. It was found that columbianetin acetate was rapidly and widely distributed in rats, and eliminated rapidly from plasma. Columbianetin acetate could be metabolized into columbianetin in vivo. The absolute bioavailability of pure columbianetin acetate is 7.0 ± 4.3%. Other co-existing ingredients in the APR extract could increase the concentration of its metabolite columbianetin in plasma and this was caused by columbianetin-β-D-glucopyranoside. Cumulative excretion of columbianetin acetate in urine accounted for 0.0109 ± 0.0067% of the total dosage. The cumulative amounts of columbianetin acetate in the feces account for 9.32 ± 6.63% of the total dose. Columbianetin acetate was mainly excreted in the feces.

A network pharmacology-integrated metabolomics strategy for clarifying the difference between effective compounds of raw and processed Farfarae flos by ultra high-performance liquid chromatography-quadrupole-time of flight mass spectrometry

Graphical abstract Figure. No caption available. HighlightsThe network pharmacology integrated metabolomics strategy was reported.Clarifying the difference of effective compounds between raw and processed Farfarae flos.Raw and processed Farfarae flos was distinguished.Chlorogenic acid, caffeic acid, rutin and isoquercitrin were the difference between raw and processed Farfarae flos. ABSTRACT This study aimed to clarify the difference between the effective compounds of raw and processed Farfarae flos using a network pharmacology‐integrated metabolomics strategy. First, metabolomics data were obtained by ultra high‐performance liquid chromatography‐quadrupole‐time of flight mass spectrometry (UHPLC‐Q‐TOF/MS). Then, metabolomics analysis was developed to screen for the influential compounds that were different between raw and processed Farfarae flos. Finally, a network pharmacology approach was applied to verify the activity of the screened compounds. As a result, 4 compounds (chlorogenic acid, caffeic acid, rutin and isoquercitrin) were successfully screened, identified, quantified and verified as the most influential effective compounds. They may synergistically inhibit the p38, JNK and ERK‐mediated pathways, which would induce the inhibition of the expression of the IFA virus. The results revealed that the proposed network pharmacology‐integrated metabolomics strategy was a powerful tool for discovering the effective compounds that were responsible for the difference between raw and processed Chinese herbs.

Screening of Combinatorial Quality Markers for Natural Products by Metabolomics Coupled With Chemometrics. A Case Study on Pollen Typhae

Natural products, especially for traditional Chinese medicines (TCMs), are of great importance to cure diseases. Yet it was hard to screen the influential quality markers for monitoring the quality. A simple and comprehensive strategy was developed and validated to screen for the combinatorial quality markers for precise quality evaluation and discrimination of natural products. In this study, Pollen Typhae (PT) and its processed products carbonized PT were selected as the representative case. Firstly, metabolomics data of 49 batches crude PT and carbonized PT was obtained by ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Then, metabolomics approaches were performed to screen for the potential markers that lead to the quality difference. Finally, chemometric methods were used to validate the accuracy of combinatorial quality markers. Thus, 42 compounds were identified from PT, 5 markers (isorhamnetin-3-O-(2G-α-L-rhamnosyl)-rutinoside, isorhamnetin-3-O-neohesperidoside, astragalin, kaempferol and umbelliferone) were successfully screened, identified, quantified and regarded as combinatorial quality markers for precise quality evaluation of crude and carbonized PT. It was demonstrated that the established comprehensively strategy provide an efficient tool for precise quality evaluation of natural products from the whole.

An activity-integrated strategy of the identification, screening and determination of potential neuraminidase inhibitors from Radix Scutellariae

Small molecules isolated from herbal medicines (HMs) were identified as the potential neuraminidase inhibitors which are effective in influenza prevention and treatment. Unfortunately, current available screen methods of small molecules isolated from HMs are inefficient and insensitive. Here a novel Ultra Performance Liquid Chromatography coupled with diode-array detectors and auto-fraction collector / time-of-flight mass spectrometry (UPLC-DAD-FC/Q-TOF-MS) screening method with high efficiency was developed and validated to separate, collect, enrich, identify and quantify potential neuraminidase inhibitors from Radix Scutellariae. The results showed that 26 components with neuraminidase inhibitory activity were identified from Radix Scutellariae extracts. It was also found that the influence of origins on the quality of RS was more than that of cultivated time on the basis of the concentration of the effective components. These results brought novel insights into quality evaluation of Radix Scutellariae. It was demonstrated that new activity-integrated strategy was a suitable technique for the identification, screening and determination of potential neuraminidase inhibitors in herbal medicine and will provide novel potential strategies in other drug screening from herbal medicine.