Three-dimensional(3D)cell spheroid models combined with mass spectrometry imaging(MSI)enables innovative investigation of in vivo-like biological processes under different physiological and pathological conditions.Her...Three-dimensional(3D)cell spheroid models combined with mass spectrometry imaging(MSI)enables innovative investigation of in vivo-like biological processes under different physiological and pathological conditions.Herein,airflow-assisted desorption electrospray ionization-MSI(AFADESI-MSI)was coupled with 3D HepG2 spheroids to assess the metabolism and hepatotoxicity of amiodarone(AMI).High-coverage imaging of>1100 endogenous metabolites in hepatocyte spheroids was achieved using AFADESI-MSI.Following AMI treatment at different times,15 metabolites of AMI involved in Ndesethylation,hydroxylation,deiodination,and desaturation metabolic reactions were identified,and according to their spatiotemporal dynamics features,the metabolic pathways of AMI were proposed.Subsequently,the temporal and spatial changes in metabolic disturbance within spheroids caused by drug exposure were obtained via metabolomic analysis.The main dysregulated metabolic pathways included arachidonic acid and glycerophospholipid metabolism,providing considerable evidence for the mechanism of AMI hepatotoxicity.In addition,a biomarker group of eight fatty acids was selected that provided improved indication of cell viability and could characterize the hepatotoxicity of AMI.The combination of AFADESI-MSI and HepG2 spheroids can simultaneously obtain spatiotemporal information for drugs,drug metabolites,and endogenous metabolites after AMI treatment,providing an effective tool for in vitro drug hepatotoxicity evaluation.展开更多
Because of the randomness of wind power and photovoltaic(PV)output of new energy bases,the problem of peak regulation capability and voltage stability of ultra-high voltage direct current(UHVDC)transmission lines,we p...Because of the randomness of wind power and photovoltaic(PV)output of new energy bases,the problem of peak regulation capability and voltage stability of ultra-high voltage direct current(UHVDC)transmission lines,we proposed an optimum allocation method of installed capacity of the solar-thermal power station based on chance constrained programming in this work.Firstly,we established the uncertainty model of wind power and PV based on the chance constrained planning theory.Then we used the K-medoids clusteringmethod to cluster the scenarios considering the actual operation scenarios throughout the year.Secondly,we established the optimal configuration model based on the objective function of the strongest transient voltage stability and the lowest overall cost of operation.Finally,by quantitative analysis of actual wind power and photovoltaic new energy base,this work verified the feasibility of the proposed method.As a result of the simulations,we found that using the optimal configuration method of solar-thermal power stations could ensure an accurate allocation of installed capacity.When the installed capacity of the solar-thermal power station is 1×106 kW,the transient voltage recovery index(TVRI)is 0.359,which has a strong voltage support capacity for the system.Based on the results of this work,the optimal configuration of the installed capacity of the solar-thermal power plant can improve peak shaving performance,transient voltage support capability,and new energy consumption while satisfying the Direct Current(DC)outgoing transmission premise.展开更多
In vitro experiments have demonstrated that neuronal-like cells derived from bone marrow mesen- chymal stem cells can survive, migrate, integrate and help to restore the function and behaviors of spinal cord injury mo...In vitro experiments have demonstrated that neuronal-like cells derived from bone marrow mesen- chymal stem cells can survive, migrate, integrate and help to restore the function and behaviors of spinal cord injury models, and that they may serve as a suitable approach to treating spinal cord injury. However, it is very difficult to track transplanted cells in vivo. In this study, we injected su- perparamagnetic iron oxide-labeled neuronal-like cells into the subarachnoid space in a rabbit model of spinal cord injury. At 7 days after cell transplantation, a small number of dot-shaped low signal intensity shadows were observed in the spinal cord injury region, and at 14 days, the number of these shadows increased on T2-weighted imaging. Perl＇s Prussian blue staining detected dot-shaped low signal intensity shadows in the spinal cord injury region, indicative of superpara- magnetic iron oxide nanoparticle-labeled cells. These findings suggest that transplanted neu- ronal-like cells derived from bone marrow mesenchymal stem cells can migrate to the spinal cord injury region and can be tracked by magnetic resonance in vivo. Magnetic resonance imaging represents an efficient noninvasive technique for visually tracking transplanted cells in vivo.展开更多
Due to its low volatile characteristics of lean coal,it is difficult to catch fire and burn out.Therefore,high temperature is needed to maintain combustion efficiency,while,this leads to high nitrogen oxide emission.F...Due to its low volatile characteristics of lean coal,it is difficult to catch fire and burn out.Therefore,high temperature is needed to maintain combustion efficiency,while,this leads to high nitrogen oxide emission.For power plant boilers burning lean coal,stable combustion with lower nitrogen oxide emission is a challenging task.This study applied the 3D numerical simulation on the analysis of a novel de-coupling burner for low-volatile coal and its structure and operation parameters optimization.Results indicate that although it was more difficult for lean coal decoupling burner to ignite lean coal than high volatile coal,the burner formed a stepwise ignition trend,which promoted the rapid ignition of lean coal.Comparison of three central partition plate structure shows that in terms of characteristics of the flow field distribution,rich and lean separation and combustion,the structure with an inclination of 0°showed good performance,with its rich-lean air ratio being 0.85 and concentration ratio being 22.94,and there was an apparent decoupling combustion characteristic.Finally,the structure of the selected burner was optimized for its operational conditions.The optimal operating parameters was determined as the primary air velocity of 24.9 m·s^-1 and the mass flow rate of pulverized coal of 2.5 kg·s^-1,in which the pyrolysis products were utilized as reductive agent more fully.Eventually,the nitrogen oxide was efficiently reduced to nitrogen,which emission concentration was 61.88%lower than that in the design condition.展开更多
Aiming at the low spatial resolution of meteorological data output from a numerical model in photovoltaic power prediction,a geographically weighted statistical downscaling method considers the influence factors such ...Aiming at the low spatial resolution of meteorological data output from a numerical model in photovoltaic power prediction,a geographically weighted statistical downscaling method considers the influence factors such as normalized vegetation index(NDVI),digital elevation model(DEM),slope direction,longitude and latitude is proposed.This method is based on the correlation between meteorological data and NDVI,DEM,slope direction,latitude and longitude,and introduces DEM and local Moran index to improve the regression model,and obtains 100∗100 m high-resolution meteorological spatial distribution data.Finally,combining the measured data of the study area and the established EOF iterative downscaling method to verify and compare the downscaling results.The results show that the error between the downscaled meteorological data and the measured value is smaller,and the comprehensive downscaling accuracy of the geographically weighted regression method is higher,and the model fitting effect is better.Therefore,this method can effectively improve the influence of errors caused by lower resolution,and provide a more reliable meteorological basis for the prediction of photovoltaic power.展开更多
Deconvolution of potential drug targets of the central nervous system(CNS)is particularly challenging because of the complicated structure and function of the brain.Here,a spatiotemporally resolved metabolomics and is...Deconvolution of potential drug targets of the central nervous system(CNS)is particularly challenging because of the complicated structure and function of the brain.Here,a spatiotemporally resolved metabolomics and isotope tracing strategy was proposed and demonstrated to be powerful for deconvoluting and localizing potential targets of CNS drugs by using ambient mass spectrometry imaging.This strategy can map various substances including exogenous drugs,isotopically labeled metabolites,and various types of endogenous metabolites in the brain tissue sections to illustrate their microregional distribution pattern in the brain and locate drug action-related metabolic nodes and pathways.The strategy revealed that the sedative-hypnotic drug candidate YZG-331 was prominently distributed in the pineal gland and entered the thalamus and hypothalamus in relatively small amounts,and can increase glutamate decarboxylase activity to elevateγ-aminobutyric acid(GABA)levels in the hypothalamus,agonize organic cation transporter 3 to release extracellular histamine into peripheral circulation.These findings emphasize the promising capability of spatiotemporally resolved metabolomics and isotope tracing to help elucidate the multiple targets and the mechanisms of action of CNS drugs.展开更多
On-tissue chemical derivatization(OTCD)effectively enhances ionization efficiency of low abundant and poorly ionized functional molecules to improve detection sensitivity and coverage of mass spectrometry imaging(MSI)...On-tissue chemical derivatization(OTCD)effectively enhances ionization efficiency of low abundant and poorly ionized functional molecules to improve detection sensitivity and coverage of mass spectrometry imaging(MSI).Combination OTCD and MSI provides a novel strategy for visualizing previously undisclosed metabolic heterogeneity in tumor.Herein,we present a method to visualize heterogeneous metabolism of oxylipins within tumor by coupling OTCD with airflow-assisted desorption electrospray ionization(AFADESI)-MSI.Taking Girard’s P as a derivatization reagent,easily ionized hydrazide and quaternary amine groups were introduced into the structure of carbonyl metabolites via condensation reaction.Oxylipins,including 127 fatty aldehydes(FALs)and 71 oxo fatty acids(FAs),were detected and imaged in esophageal cancer xenograft with AFADESI-MSI after OTCD.Then t-distributed stochastic neighbor embedding and random forest were exploited to precisely locate the distribution of oxylipins in heterogeneous tumor tissue.With this method,we surprisingly found almost all FALs and oxo FAs significantly accumulated in the core region of tumor,and exhibited a gradual increase trend in tumor over time.These results reveal spatiotemporal heterogeneity of oxylipins in tumor progression,highlighting the value of OTCD combined with MSI to gain deeper insights into understanding tumor metabolism.展开更多
With the rapid development and wide application of traditional Chinese medicine injection(TCMI), a number of adverse events of some TCMIs have incessantly been reported and have drawn broad attention in recent years. ...With the rapid development and wide application of traditional Chinese medicine injection(TCMI), a number of adverse events of some TCMIs have incessantly been reported and have drawn broad attention in recent years. Establishing effective and practical analytical methods for safety evaluation and quality control of TCMI can help to improve the safety of TCMIs in clinical applications. In this study, a sensitive and rapid high-performance liquid chromatography–tandem mass spectrometry(HPLC–MS/MS)method has been developed and validated for the quantitative determination of potentially harmful substance5,5′-oxydimethylenebis(2-furfural, OMBF) in TCMI samples. Chromatographic separation was performed on a C18 reversed-phase column(150 mm × 2.1 mm, 5 μm) by gradient elution, using methanol–water containing 0.1% formic acid as mobile phase at the flow rate of 0.3 m L/min. MS/MS detection was performed on a triple quadrupole mass spectrometer with positive electrospray ionization in the multiple reaction-monitoring mode. The method was sensitive with a limit of quantification of 0.3 ng/m L and linear over the range of 0.3–30 ng/m L(r = 0.9998). Intra-and inter-day precision for analyte was o9.52% RSD withrecoveries in the range 88.0–109.67% at three concentration levels. The validated method was successfully applied to quantitatively determine the compound OMBF in TCMIs and glucose injections. Our study indicates that this method is simple, sensitive, practicable and reliable, and could be applied for safety evaluation and quality control of TCMIs and glucose injections.展开更多
Mass spectrometry imaging (MSI) technology can simultaneously obtain the spatial distribution of thousands of chemical compounds and has unique advantages compared to other techniques that allow mapping the surface of...Mass spectrometry imaging (MSI) technology can simultaneously obtain the spatial distribution of thousands of chemical compounds and has unique advantages compared to other techniques that allow mapping the surface of bio-tissue. Here, we combined an air flow-assisted desorption electrospray ionization (AFADESI) MSI device with a high-resolution mass spectrometer to optimize the system parameters and achieve more accurate spatial distribution characteristics for compounds of interest while investigating bio-tissue sections. The platform set-up, required instrumentation, sample pretreatment, parameter optimization and bio-tissue characterization are described and discussed.Finally, the parameter conditions that can provide optimal ionic intensity and enhanced resolution were confirmed. The reasonable resolution and sensitivity improvements of AFADESI-MSI have been achieved through tandem a high-resolution mass spectrometer system, therefore, it would be a promising technique for the bio-tissue imaging analysis.展开更多
A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry（UPLC–MS/MS） method was developed and fully validated for determination of arformoterol in rat plasma, lung and trachea tissues....A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry（UPLC–MS/MS） method was developed and fully validated for determination of arformoterol in rat plasma, lung and trachea tissues. The chromatographic separation was performed on an Agilent XDB C8 column with gradient elution by using acetonitrile and 0.1% formic acid water. The method presented high sensitivity（LLOQ of 1.83 pg/mL for plasma and 3.90 pg/mL for lung and trachea tissue homogenates） and great linearity over the range of 1.83–458 pg/mL for plasma, 13.9–1560 pg/mL for lung and trachea tissue homogenates. No carry over effect and matrix effect were observed. The intra-and inter-day precision/accuracy were within ±15% at three quality control concentration levels. This robust method was successfully applied to the pharmacokinetic, lung and trachea tissue distribution study after inhalation administration of arformoterol tartrate inhalation solution（50 m g/kg）. The in vivo information indicate that arformoterol can be rapidly absorbed into blood through respiratory systems, lung and trachea tissue maintain a certain amount of arformoterol in 1 h after dosing.展开更多
基金funded by the National Natural Science Foundation of China(Grant No.:21874156)the Chinese Academy of Medical Science(CAMS)Innovation Fund for Medical Sciences(Grant No.:2021-1-I2M-028).
文摘Three-dimensional(3D)cell spheroid models combined with mass spectrometry imaging(MSI)enables innovative investigation of in vivo-like biological processes under different physiological and pathological conditions.Herein,airflow-assisted desorption electrospray ionization-MSI(AFADESI-MSI)was coupled with 3D HepG2 spheroids to assess the metabolism and hepatotoxicity of amiodarone(AMI).High-coverage imaging of>1100 endogenous metabolites in hepatocyte spheroids was achieved using AFADESI-MSI.Following AMI treatment at different times,15 metabolites of AMI involved in Ndesethylation,hydroxylation,deiodination,and desaturation metabolic reactions were identified,and according to their spatiotemporal dynamics features,the metabolic pathways of AMI were proposed.Subsequently,the temporal and spatial changes in metabolic disturbance within spheroids caused by drug exposure were obtained via metabolomic analysis.The main dysregulated metabolic pathways included arachidonic acid and glycerophospholipid metabolism,providing considerable evidence for the mechanism of AMI hepatotoxicity.In addition,a biomarker group of eight fatty acids was selected that provided improved indication of cell viability and could characterize the hepatotoxicity of AMI.The combination of AFADESI-MSI and HepG2 spheroids can simultaneously obtain spatiotemporal information for drugs,drug metabolites,and endogenous metabolites after AMI treatment,providing an effective tool for in vitro drug hepatotoxicity evaluation.
基金funded by Major Science and Technology Projects in Gansu Province(19ZD2GA003).
文摘Because of the randomness of wind power and photovoltaic(PV)output of new energy bases,the problem of peak regulation capability and voltage stability of ultra-high voltage direct current(UHVDC)transmission lines,we proposed an optimum allocation method of installed capacity of the solar-thermal power station based on chance constrained programming in this work.Firstly,we established the uncertainty model of wind power and PV based on the chance constrained planning theory.Then we used the K-medoids clusteringmethod to cluster the scenarios considering the actual operation scenarios throughout the year.Secondly,we established the optimal configuration model based on the objective function of the strongest transient voltage stability and the lowest overall cost of operation.Finally,by quantitative analysis of actual wind power and photovoltaic new energy base,this work verified the feasibility of the proposed method.As a result of the simulations,we found that using the optimal configuration method of solar-thermal power stations could ensure an accurate allocation of installed capacity.When the installed capacity of the solar-thermal power station is 1×106 kW,the transient voltage recovery index(TVRI)is 0.359,which has a strong voltage support capacity for the system.Based on the results of this work,the optimal configuration of the installed capacity of the solar-thermal power plant can improve peak shaving performance,transient voltage support capability,and new energy consumption while satisfying the Direct Current(DC)outgoing transmission premise.
基金supported by a grant from Science and Technology Research Projects of Shanxi Province,No.20120321028-02a grant from the Scientific and Technical Foundation of Shanxi Provincial Health Department,No.201201067+1 种基金a grant from University Research and Development Projects of Shanxi Province,No.20131101grant from the National Natural Science Foundation of China,No.81371628
文摘In vitro experiments have demonstrated that neuronal-like cells derived from bone marrow mesen- chymal stem cells can survive, migrate, integrate and help to restore the function and behaviors of spinal cord injury models, and that they may serve as a suitable approach to treating spinal cord injury. However, it is very difficult to track transplanted cells in vivo. In this study, we injected su- perparamagnetic iron oxide-labeled neuronal-like cells into the subarachnoid space in a rabbit model of spinal cord injury. At 7 days after cell transplantation, a small number of dot-shaped low signal intensity shadows were observed in the spinal cord injury region, and at 14 days, the number of these shadows increased on T2-weighted imaging. Perl＇s Prussian blue staining detected dot-shaped low signal intensity shadows in the spinal cord injury region, indicative of superpara- magnetic iron oxide nanoparticle-labeled cells. These findings suggest that transplanted neu- ronal-like cells derived from bone marrow mesenchymal stem cells can migrate to the spinal cord injury region and can be tracked by magnetic resonance in vivo. Magnetic resonance imaging represents an efficient noninvasive technique for visually tracking transplanted cells in vivo.
基金supported by National Natural Science Foundation of China—Shanxi coal based low carbon joint fund(U1610254)Shanxi Province Basic Applied Research Youth Fund(201801D221345)2018 Xiangyuan County Solid Waste Comprehensive Utilization Science and Technology Projects(2018XYSDYY-14)。
文摘Due to its low volatile characteristics of lean coal,it is difficult to catch fire and burn out.Therefore,high temperature is needed to maintain combustion efficiency,while,this leads to high nitrogen oxide emission.For power plant boilers burning lean coal,stable combustion with lower nitrogen oxide emission is a challenging task.This study applied the 3D numerical simulation on the analysis of a novel de-coupling burner for low-volatile coal and its structure and operation parameters optimization.Results indicate that although it was more difficult for lean coal decoupling burner to ignite lean coal than high volatile coal,the burner formed a stepwise ignition trend,which promoted the rapid ignition of lean coal.Comparison of three central partition plate structure shows that in terms of characteristics of the flow field distribution,rich and lean separation and combustion,the structure with an inclination of 0°showed good performance,with its rich-lean air ratio being 0.85 and concentration ratio being 22.94,and there was an apparent decoupling combustion characteristic.Finally,the structure of the selected burner was optimized for its operational conditions.The optimal operating parameters was determined as the primary air velocity of 24.9 m·s^-1 and the mass flow rate of pulverized coal of 2.5 kg·s^-1,in which the pyrolysis products were utilized as reductive agent more fully.Eventually,the nitrogen oxide was efficiently reduced to nitrogen,which emission concentration was 61.88%lower than that in the design condition.
基金supported by the Science and Technology project of StateGridGansu Electric Power Company(No.52272219002).
文摘Aiming at the low spatial resolution of meteorological data output from a numerical model in photovoltaic power prediction,a geographically weighted statistical downscaling method considers the influence factors such as normalized vegetation index(NDVI),digital elevation model(DEM),slope direction,longitude and latitude is proposed.This method is based on the correlation between meteorological data and NDVI,DEM,slope direction,latitude and longitude,and introduces DEM and local Moran index to improve the regression model,and obtains 100∗100 m high-resolution meteorological spatial distribution data.Finally,combining the measured data of the study area and the established EOF iterative downscaling method to verify and compare the downscaling results.The results show that the error between the downscaled meteorological data and the measured value is smaller,and the comprehensive downscaling accuracy of the geographically weighted regression method is higher,and the model fitting effect is better.Therefore,this method can effectively improve the influence of errors caused by lower resolution,and provide a more reliable meteorological basis for the prediction of photovoltaic power.
基金supported by the National Natural Science Foundation of China(No.21927808 and No.81974500)Chinese Academy of Medical Science(CAMS)Innovation Fund for Medical Sciences(CIFMS,No.2022-I2M-2-002 and 2021-1I2M-028,China)。
文摘Deconvolution of potential drug targets of the central nervous system(CNS)is particularly challenging because of the complicated structure and function of the brain.Here,a spatiotemporally resolved metabolomics and isotope tracing strategy was proposed and demonstrated to be powerful for deconvoluting and localizing potential targets of CNS drugs by using ambient mass spectrometry imaging.This strategy can map various substances including exogenous drugs,isotopically labeled metabolites,and various types of endogenous metabolites in the brain tissue sections to illustrate their microregional distribution pattern in the brain and locate drug action-related metabolic nodes and pathways.The strategy revealed that the sedative-hypnotic drug candidate YZG-331 was prominently distributed in the pineal gland and entered the thalamus and hypothalamus in relatively small amounts,and can increase glutamate decarboxylase activity to elevateγ-aminobutyric acid(GABA)levels in the hypothalamus,agonize organic cation transporter 3 to release extracellular histamine into peripheral circulation.These findings emphasize the promising capability of spatiotemporally resolved metabolomics and isotope tracing to help elucidate the multiple targets and the mechanisms of action of CNS drugs.
基金supported by the National Natural Science Foundation of China(No.21927808)the Chinese Academy of Medical Science(CAMS)Innovation Fund for Medical Sciences(CIFMS,Nos.2022-I2M-2-002 and 2021-1-I2M-028).
文摘On-tissue chemical derivatization(OTCD)effectively enhances ionization efficiency of low abundant and poorly ionized functional molecules to improve detection sensitivity and coverage of mass spectrometry imaging(MSI).Combination OTCD and MSI provides a novel strategy for visualizing previously undisclosed metabolic heterogeneity in tumor.Herein,we present a method to visualize heterogeneous metabolism of oxylipins within tumor by coupling OTCD with airflow-assisted desorption electrospray ionization(AFADESI)-MSI.Taking Girard’s P as a derivatization reagent,easily ionized hydrazide and quaternary amine groups were introduced into the structure of carbonyl metabolites via condensation reaction.Oxylipins,including 127 fatty aldehydes(FALs)and 71 oxo fatty acids(FAs),were detected and imaged in esophageal cancer xenograft with AFADESI-MSI after OTCD.Then t-distributed stochastic neighbor embedding and random forest were exploited to precisely locate the distribution of oxylipins in heterogeneous tumor tissue.With this method,we surprisingly found almost all FALs and oxo FAs significantly accumulated in the core region of tumor,and exhibited a gradual increase trend in tumor over time.These results reveal spatiotemporal heterogeneity of oxylipins in tumor progression,highlighting the value of OTCD combined with MSI to gain deeper insights into understanding tumor metabolism.
基金supported by Chinese Academy of Medical Science (CAMS) Innovation Fund for Medical Sciences (Grant Nos. 2016-I2M-1–009 and 2016-I2M-3–010)National Scientific and Technological Major Project for New Drugs (Grant No. 2017ZX09101003-002-004)
文摘With the rapid development and wide application of traditional Chinese medicine injection(TCMI), a number of adverse events of some TCMIs have incessantly been reported and have drawn broad attention in recent years. Establishing effective and practical analytical methods for safety evaluation and quality control of TCMI can help to improve the safety of TCMIs in clinical applications. In this study, a sensitive and rapid high-performance liquid chromatography–tandem mass spectrometry(HPLC–MS/MS)method has been developed and validated for the quantitative determination of potentially harmful substance5,5′-oxydimethylenebis(2-furfural, OMBF) in TCMI samples. Chromatographic separation was performed on a C18 reversed-phase column(150 mm × 2.1 mm, 5 μm) by gradient elution, using methanol–water containing 0.1% formic acid as mobile phase at the flow rate of 0.3 m L/min. MS/MS detection was performed on a triple quadrupole mass spectrometer with positive electrospray ionization in the multiple reaction-monitoring mode. The method was sensitive with a limit of quantification of 0.3 ng/m L and linear over the range of 0.3–30 ng/m L(r = 0.9998). Intra-and inter-day precision for analyte was o9.52% RSD withrecoveries in the range 88.0–109.67% at three concentration levels. The validated method was successfully applied to quantitatively determine the compound OMBF in TCMIs and glucose injections. Our study indicates that this method is simple, sensitive, practicable and reliable, and could be applied for safety evaluation and quality control of TCMIs and glucose injections.
基金supported by the National Instrumentation Program (No. 2016YFF0100304)the National Natural Science Foundation of China(Nos. 21335007, 81773678)+1 种基金the CAMS Innovation Fund for Medical Sciences(No. 2016-12 M-1-009)PUMC Youth Fund and the Fundamental Research Funds for the Central Universities(No. 3332015177)
文摘Mass spectrometry imaging (MSI) technology can simultaneously obtain the spatial distribution of thousands of chemical compounds and has unique advantages compared to other techniques that allow mapping the surface of bio-tissue. Here, we combined an air flow-assisted desorption electrospray ionization (AFADESI) MSI device with a high-resolution mass spectrometer to optimize the system parameters and achieve more accurate spatial distribution characteristics for compounds of interest while investigating bio-tissue sections. The platform set-up, required instrumentation, sample pretreatment, parameter optimization and bio-tissue characterization are described and discussed.Finally, the parameter conditions that can provide optimal ionic intensity and enhanced resolution were confirmed. The reasonable resolution and sensitivity improvements of AFADESI-MSI have been achieved through tandem a high-resolution mass spectrometer system, therefore, it would be a promising technique for the bio-tissue imaging analysis.
基金supported by CAMS Innovation Fund for Medical Sciences(No. 2016-12M-1-009)National Scientific and Technological Major Project for New Drugs(No.2017ZX09101003-002-004)
文摘A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry（UPLC–MS/MS） method was developed and fully validated for determination of arformoterol in rat plasma, lung and trachea tissues. The chromatographic separation was performed on an Agilent XDB C8 column with gradient elution by using acetonitrile and 0.1% formic acid water. The method presented high sensitivity（LLOQ of 1.83 pg/mL for plasma and 3.90 pg/mL for lung and trachea tissue homogenates） and great linearity over the range of 1.83–458 pg/mL for plasma, 13.9–1560 pg/mL for lung and trachea tissue homogenates. No carry over effect and matrix effect were observed. The intra-and inter-day precision/accuracy were within ±15% at three quality control concentration levels. This robust method was successfully applied to the pharmacokinetic, lung and trachea tissue distribution study after inhalation administration of arformoterol tartrate inhalation solution（50 m g/kg）. The in vivo information indicate that arformoterol can be rapidly absorbed into blood through respiratory systems, lung and trachea tissue maintain a certain amount of arformoterol in 1 h after dosing.
