A simple,rapid and reliable liquid chromatography–mass spectrometry method for determination of methotrexate in human plasma and its application to therapeutic drug monitoring

A simple, rapid and reliable liquid chromatography–electrospray ionization tandem mass spectrometry method was established and validated for the determination of methotrexate in human plasma. After a straightforward protein precipitation by acetonitrile–water (70:30, v/v), methotrexate (MTX) and p‐aminoacetophenone (used as internal standard, IS) were separated on a Column C₁₈ column (50 × 2.1 mm, 3 µm; Column Technology, Fremont, CA, USA) using a gradient elution with mobile phase of acetonitrile and 0.03% acetic acid aqueous solution at a flow rate of 0.5 mL/min. The total chromatographic runtime was 5 min for each injection. Quantification detection was performed in a triple‐quadruple tandem mass spectrometer under positive mode monitoring the following mass transitions: m/z 455.3 → 308.3 for MTX and m/z 136.1 → 94.4 for IS. The calibration curve was linear over the range of 0.05–25.0 µmol/L with a lower limit of quantification of 0.05 µmol/L. The intra‐ and interday precisions were <5.2%, the accuracy varied from ?4.1 to 4.5%. The recovery was >94%. The LC‐MS/MS method showed an excellent agreement with the existing HPLC‐UV method using Passing–Bablok regression and Bland–Altman difference plot analysis. The validated LC‐MS/MS can be successfully applied to the routine therapeutic drug monitoring of MTX in clinical laboratories. Copyright © 2015 John Wiley & Sons, Ltd.     

“Self-repairing” nanoshell for cell protection

Self-repair is nature''s way of protecting living organisms. However, most single cells are inherently less capable of self-repairing, which greatly limits their wide applications. Here, we present a self-assembly approach to create a nanoshell around the cell surface using nanoporous biohybrid aggregates. The biohybrid shells present self-repairing behaviour, resulting in high activity and extended viability of the encapsulated cells (eukaryotic and prokaryotic cells) in harsh micro-environments, such as under UV radiation, natural toxin invasion, high-light radiation and abrupt pH-value changes. Furthermore, an interaction mechanism is proposed and studied, which is successful to guide design and synthesis of self-repairing biohybrid shells using different bioactive molecules.     

In Situ Synthesis and Characterization of Poly(aryleneethynylene)‐Grafted Reduced Graphene Oxide

Using highly soluble bromo‐functionalized reduced graphene oxide (RGBr) as a key graphene template for surface‐directing Sonogashira–Hagihara polymerization, a novel soluble poly(arylene‐ethynylene)‐grafted reduced graphene oxide, hereafter abbreviated as PAE‐g‐RGO, was prepared in situ. The entirely different electron distribution of LUMO and HOMO of PAE‐g‐RGO suggested the existence of a charge‐transfer (CT) state (PAE^.?–RGO^.+). The negative ΔG_CS value (?2.57 eV) indicates that the occurrence of the charge separation via ¹RGO* in o‐DCB is exothermic and favorable. Upon irradiation with 365 nm light, the light‐induced electron paramagnetic resonance (LEPR) spectrum of PAE‐g‐RGO showed a decrease in the spin‐state density owing to photoinduced intramolecular electron transfer events in this system. A sandwich‐type Al/PAE‐g‐RGO/ITO device showed representative bistable electrical switching behavior. The nonvolatile memory performance was attributed to the CT‐induced conductance changes, which was supported by molecular computation results and conductive atomic force microscopy (C‐AFM) images.     

1.3 GHz超导腔磁通排出效应研究

设计并搭建了一套高精度的磁场测量和补偿系统,并结合中国科学院高能物理研究所(IHEP)的2K超导腔垂直测试平台对1.3 GHz单加速间隙超导腔的磁通排出效应开展了实验研究:利用研制的磁场测量和补偿系统能够精密地测量超导腔赤道位置磁场,并能够将磁场补偿至小于5.0×10-8 T;并对超导腔不同表面温度梯度下的磁通排出效应进行了测量分析;对钉扎了磁场的超导腔进行了射频性能测试,研究了超导腔电阻对磁通钉扎的敏感度,以及在不同电场梯度下超导腔的表面电阻变化情况。结果表明,研制的高精度磁场测量和补偿系统能够满足超导腔磁通排出研究的需求;高的超导腔表面温度梯度有利于磁通的排出;磁通钉扎电阻的敏感度随着加速电场梯度的增加而增大,导致超导腔的性能下降。此实验研究也为后续超导腔的研制奠定了一定基础。     

Serum pharmacochemistry combined with multiple data processing approach to screen the bioactive components and their metabolites in Mutan Cortex by ultra‐performance liquid chromatography tandem mass spectrometry

Root cortex of Paeonia suffruticosa Andrews (Paeoniaceae), known as Moutan Cortex (MC), is known to have anti‐allergic and anti‐inflammatory properties. However, the constituents absorbed into blood after oral administration of MC remain unknown. A sensitive and rapid method by ultra‐high‐pressure liquid chromatography–electrospray ionization–quadrupole‐time‐of‐flight mass spectrometry (UPLC‐ESI‐Q‐TOF‐MS) technology and the MetaboLynx^TM software combined with multiple data processing approach (Mdpa) was established to investigate the absorbed constituents in rats after oral administration of MC, providing unique high‐throughput capabilities for drug metabolism study. A hyphenated electrospray ionization and quadrupole‐time‐of‐flight analyzer was used for the determination of accurate mass of the fragment ion in negative mode, with excellent MS mass accuracy and enhanced data acquisition. This rapid automated analysis method was successfully applied for screening and identification of the constituents absorbed and metabolized studies of MC after oral administration to rats. A total of 46 peaks were obtained from MC, 41 of which were tentatively characterized. In the VIP‐plot of orthogonal partial least‐squares discriminant analysis, 23 interesting ions in serum samples were extracted, and 16 parent components and seven metabolites were detected in vivo. The integrative serum pharmacochemistry technique, UPLC‐ESI‐Q‐TOF‐MS, and Mdpa method were successfully applied for rapid discovery of multiple components from MC. Copyright © 2013 John Wiley & Sons, Ltd.