Quasi-MSn identification of flavanone 7-glycoside isomers in Da Chengqi Tang by high performance liquid chromatography-tandem mass spectrometry

<p>Abstract</p> <p>Background</p> <p><it>Da Chengqi Tang </it>(DCT) is a common purgative formula in Chinese medicine. Flavanones are its major active compounds derived from <it>Fructus Aurantii Immaturus</it>. The present study developed an LC-MS/MS method to characterize two pairs of flavanone 7-glycoside isomers, i.e., hesperidin versus neohesperidin and naringin versus isonaringin.</p> <p>Methods</p> <p>After solid phase purification, components in sample were separated on a Agilent zorbax SB-C18 (5 μm, 250 mm × 4.6 mm) analytical column. ESI-MS and quasi-MSⁿwere performed in negative ion mode to obtain structural data of these two pairs of flavanone 7-glycoside isomers. Moreover, UV absorption was measured.</p> <p>Results</p> <p>There was no intra-pairs difference in the UV-Vis and MS/MS spectra of the two pairs of 7-glycoside isomers, whereas the mass spectrometry fragmentation pathways between pairs were different.</p> <p>Conclusion</p> <p>The present study developed a LC-MS/MS method to explore the inter- and intra-pair difference of two pairs of flavanone 7-glycoside isomers.</p

Design of the PMT underwater cascade implosion protection system for JUNO

Photomultiplier tubes (PMTs) are widely used underwater in large-scale neutrino experiments. As a hollow glass spherelike structure, implosion is unavoidable during long-term operation under large water pressure. There is a possibility of cascade implosion to neighbor PMTs due to shockwave. Jiangmen Underground Neutrino Observatory designed a protection structure for each 20-inch PMT, consisting of a top cover, a bottom cover, and their connection. This paper introduces the requirement and design of the PMT protection system, including the material selection, investigation of manufacture technology, and prototyping. Optimization and validation by simulation and underwater experiments are also presented.Comment: 10 pages, 15 figure

Separation and determination of acetyl-glutamine enantiomers by HPLC–MS and its application in pharmacokinetic study

A high-performance liquid chromatography coupled with mass spectrometry (HPLC–MS) method was established for the separation and determination of acetyl-glutamine enantiomers (acetyl-L-glutamine and acetyl-D-glutamine) simultaneously. Baseline separation was achieved on Chiralpak AD-H column (250 mm × 4.6 mm, 5 µm). n-Hexane (containing 0.1% acetic acid) and ethanol (75:25, v/v) were used as mobile phase at a flow rate of 0.6 mL/min. The detection was operated in the negative ion mode with an ESI source. [M-H]− m/z 187.0540 for enantiomers and [M-H]− m/z 179.0240 for aspirin (IS) were selected as detecting ions. The linear range of the calibration curve for each enantiomer was 0.05–40 µg/mL. The precision of this method at concentrations of 0.5–20 µg/mL was within 7.23%, and the accuracy was 99.81%–107.81%. The precision at LOQ (0.05 µg/mL) was between 16.28% and 17.56%, which was poor than that at QC levels. The average extraction recovery was higher than 85% for both enantiomers at QC levels. The pharmacokinetics of enantiomers was found to be stereoselective. There was not chiral inversion in vivo or in vitro between enantiomers

Determination of torasemide in human plasma and its bioequivalence study by high-performance liquid chromatography with electrospray ionization tandem mass spectrometry

A sensitive and selective method using high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC–ESI–MS) to determine the concentration of torasemide in human plasma samples was developed and validated. Tolbutamide was chosen as the internal standard (IS). The chromatography was performed on a Gl Sciences Inertsil ODS-3 column (100 mm×2.1 mm i.d., 5.0 µm) within 5 min, using methanol with 10 mM ammonium formate (60:40, v/v) as mobile phase at a flow rate of 0.2 mL/min. The targeted compound was detected in negative ionization at m/z 347.00 for torasemide and 269.00 for IS. The linearity range of this method was found to be within the concentration range of 1–2500 ng/mL (r=0.9984) for torasemide in human plasma. The accuracy of this measurement was between 94.05% and 103.86%. The extracted recovery efficiency was from 84.20% to 86.47% at three concentration levels. This method was also successfully applied in pharmacokinetics and bioequivalence studies in Chinese volunteers

Plasma Pharmacokinetics and Tissue Distribution of Doxorubicin in Rats following Treatment with Astragali Radix

Doxorubicin (DOX) is an essential component in chemotherapy, and Astragali Radix (AR) is a widely used tonic herbal medicine. The combination of DOX and AR offers widespread, well-documented advantages in treating cancer, e.g., reducing the risk of adverse effects. This study mainly aims to uncover the impact of AR on DOX disposition in vivo. Rats received a single intravenous dose of 5 mg/kg DOX following a single-dose co-treatment or multiple-dose pre-treatment of AR (10 g/kg × 1 or × 10). The concentrations of DOX in rat plasma and six tissues, including heart, liver, lung, kidney, spleen, and skeletal muscle, were determined by a fully validated LC-MS/MS method. A network-based approach was further employed to quantify the relationships between enzymes that metabolize and transport DOX and the targets of nine representative AR components in the human protein–protein interactome. We found that short-term (≤10 d) AR administration was ineffective in changing the plasma pharmacokinetics of DOX in terms of the area under the concentration–time curve (AUC, 1303.35 ± 271.74 μg/L*h versus 1208.74 ± 145.35 μg/L*h, p > 0.46), peak concentrations (Cmax, 1351.21 ± 364.86 μg/L versus 1411.01 ± 368.38 μg/L, p > 0.78), and half-life (t1/2, 31.79 ± 5.12 h versus 32.05 ± 6.95 h, p > 0.94), etc. Compared to the isotype control group, DOX concentrations in six tissues slightly decreased under AR pre-administration but only showed statistical significance (p < 0.05) in the liver. Using network analysis, we showed that five of the nine representative AR components were not localized to the vicinity of the DOX disposition-associated module. These findings suggest that AR may mitigate DOX-induced toxicity by affecting drug targets rather than drug disposition

Discovery of Synergistic Drug Combinations for Colorectal Cancer Driven by Tumor Barcode Derived from Metabolomics &ldquo;Big Data&rdquo;

The accumulation of cancer metabolomics data in the past decade provides exceptional opportunities for deeper investigations into cancer metabolism. However, integrating a large amount of heterogeneous metabolomics data to draw a full picture of the metabolic reprogramming and to discover oncometabolites of certain cancers remains challenging. In this study, a tumor barcode constructed based upon existing metabolomics &ldquo;big data&rdquo; using the Bayesian vote-counting method is proposed to identify oncometabolites in colorectal cancer (CRC). Specifically, a panel of oncometabolites of CRC was generated from 39 clinical studies with 3202 blood samples (1332 CRC vs. 1870 controls) and 990 tissue samples (495 CRC vs. 495 controls). Next, an oncometabolite-protein network was constructed by combining the tumor barcode and its involved proteins/enzymes. The effect of anti-cancer drugs or drug combinations was then mapped into this network by the random walk with restart process. Utilizing this network, potential Irinotecan (CPT-11)-sensitizing agents for CRC treatment were discovered by random forest and Xgboost. Finally, a compound named MK-2206 was highlighted and its synergy with CPT-11 was validated on two CRC cell lines. To summarize, we demonstrate in the present study that the metabolomics &ldquo;big data&rdquo;-based tumor barcodes and the subsequent network analyses are potentially useful for drug combination discovery or drug repositioning