RESULTS: Lower limit of quantitation was validated to be 15 ng/mL with a reduced sample volume of 20 μL comparing with previously reported methods. Calibration curve was linear over a concentration range of 15-2000 ng/mL. In addition to linearity, other parameters including matrix selectivity, matrix effect, recovery, method accuracy and precision, sensitivity, and stabilities of amantadine under storage conditions were also fully validated following the guidance of United States Food and Drug Administration.
{"title":"Validation of a Robust and High-Throughput HPLC-MS/MS Method to Determine Amantadine Levels in Human Plasma","authors":"K. Wank","doi":"10.17145/JAB.18.008","DOIUrl":"https://doi.org/10.17145/JAB.18.008","url":null,"abstract":"RESULTS: Lower limit of quantitation was validated to be 15 ng/mL with a reduced sample volume of 20 μL comparing with previously reported methods. Calibration curve was linear over a concentration range of 15-2000 ng/mL. In addition to linearity, other parameters including matrix selectivity, matrix effect, recovery, method accuracy and precision, sensitivity, and stabilities of amantadine under storage conditions were also fully validated following the guidance of United States Food and Drug Administration.","PeriodicalId":15014,"journal":{"name":"Journal of Applied Bioanalysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82118935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Meet our editorial board member: Dr. Jennifer Knaack","authors":"J. Knaack","doi":"10.17145/jab.18.002","DOIUrl":"https://doi.org/10.17145/jab.18.002","url":null,"abstract":"","PeriodicalId":15014,"journal":{"name":"Journal of Applied Bioanalysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91439882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A new and fully automated workflow for the cost effective drug screening of large populations based on the dried blood spot (DBS) technology was introduced in this study. DBS were prepared by spotting 15 μL of whole blood, previously spiked with alprazolam, amphetamine, cocaine, codeine, diazepam, fentanyl, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphet-amine (MDMA), methadone, methamphetamine, morphine and oxycodone onto filter paper cards. The dried spots were scanned, spiked with deuterated standards and directly extracted. The extract was transferred online to an analytical LC column and then to the electrospray ionization tandem mass spectrometry system. All drugs were quantified at their cut-off level and good precision and correlation within the calibration range was obtained. The method was finally applied to DBS samples from two patients with back pain and codeine and oxycodone could be identified and quantified accurately below the level of misuse of 89.6 ng/mL and 39.6 ng/mL respectively.
{"title":"Fully automated drug screening of dried blood spots using online LC-MS/MS analysis","authors":"Stefan Gaugler, Jana Rykl, M. Grill, V. Cebolla","doi":"10.17145/JAB.18.003","DOIUrl":"https://doi.org/10.17145/JAB.18.003","url":null,"abstract":"A new and fully automated workflow for the cost effective drug screening of large populations based on the dried blood spot (DBS) technology was introduced in this study. DBS were prepared by spotting 15 μL of whole blood, previously spiked with alprazolam, amphetamine, cocaine, codeine, diazepam, fentanyl, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphet-amine (MDMA), methadone, methamphetamine, morphine and oxycodone onto filter paper cards. The dried spots were scanned, spiked with deuterated standards and directly extracted. The extract was transferred online to an analytical LC column and then to the electrospray ionization tandem mass spectrometry system. All drugs were quantified at their cut-off level and good precision and correlation within the calibration range was obtained. The method was finally applied to DBS samples from two patients with back pain and codeine and oxycodone could be identified and quantified accurately below the level of misuse of 89.6 ng/mL and 39.6 ng/mL respectively.","PeriodicalId":15014,"journal":{"name":"Journal of Applied Bioanalysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78750398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Drexler, C. Mcnaney, Yingzi Wang, Xiaojuan Huang, M. Reily
The constantly evolving complexities of the drug discovery and development process necessitate continued advancements of supporting LC-MS bioanalytical assays by improving critical analytical figures of merit such as specificity and sensitivity along with accuracy and precision (Figure 1). The principal objective of quantitative assays is to correctly and consistently/repeatedly measure the real values thus affording quality data with high accuracy and high precision. In some cases, when only a change of the levels of endogenous compounds from baseline is monitored, an assay with low accuracy and high precision may be sufficient [1,2]. Occasionally, assays with high accuracy and low precision or even assays with low accuracy and low precision might suitable for fit-for-purpose analysis. In LC-MS bioanalysis, dry reference standards are used to prepare stock solutions followed by serial dilution to provide calibration solutions and curves against which the samples and analytes are then quantified. The analytical errors interrelated to the mass and volume measurements needed for the preparation of these solutions JOURNAL OF APPLIED BIOANALYSIS, January 2018, p. 26-31. http://dx.doi.org/10.17145/jab.18.005 (ISSN 2405-710X) Vol. 4, No. 1
药物发现和开发过程的复杂性不断发展，需要通过提高特异性、敏感性以及准确性和精密度等关键分析指标来支持LC-MS生物分析分析的持续进步(图1)。定量分析的主要目标是正确、一致/重复地测量真实值，从而提供高精度和高精度的高质量数据。在某些情况下，当仅监测内源性化合物水平与基线的变化时，低准确度和高精度的测定可能就足够了[1,2]。偶尔，准确度高、精密度低的分析方法，甚至准确度低、精密度低的分析方法，可能适合于适合目的的分析。在LC-MS生物分析中，使用干参比标准品制备原液，然后连续稀释以提供校准溶液和曲线，然后对样品和分析物进行定量。与制备这些溶液所需的质量和体积测量相关的分析误差。JOURNAL of APPLIED BIOANALYSIS, 2018年1月，第26-31页。http://dx.doi.org/10.17145/jab.18.005 (ISSN 2405-710X)第四卷，第1期
{"title":"The utility of qNMR to improve accuracy and precision of LC-MS bioanalysis","authors":"D. Drexler, C. Mcnaney, Yingzi Wang, Xiaojuan Huang, M. Reily","doi":"10.17145/JAB.18.005","DOIUrl":"https://doi.org/10.17145/JAB.18.005","url":null,"abstract":"The constantly evolving complexities of the drug discovery and development process necessitate continued advancements of supporting LC-MS bioanalytical assays by improving critical analytical figures of merit such as specificity and sensitivity along with accuracy and precision (Figure 1). The principal objective of quantitative assays is to correctly and consistently/repeatedly measure the real values thus affording quality data with high accuracy and high precision. In some cases, when only a change of the levels of endogenous compounds from baseline is monitored, an assay with low accuracy and high precision may be sufficient [1,2]. Occasionally, assays with high accuracy and low precision or even assays with low accuracy and low precision might suitable for fit-for-purpose analysis. In LC-MS bioanalysis, dry reference standards are used to prepare stock solutions followed by serial dilution to provide calibration solutions and curves against which the samples and analytes are then quantified. The analytical errors interrelated to the mass and volume measurements needed for the preparation of these solutions JOURNAL OF APPLIED BIOANALYSIS, January 2018, p. 26-31. http://dx.doi.org/10.17145/jab.18.005 (ISSN 2405-710X) Vol. 4, No. 1","PeriodicalId":15014,"journal":{"name":"Journal of Applied Bioanalysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81770300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Ghimire, K. V. Hateren, Natasha Vrubleuskaya, R. Koster, D. Touw, J. Alffenaar
A rapid liquid chromatography tandem-mass spectrometry method was developed for the determination of levofloxacin and its metabolite (desmethyl-levofloxacin) in human serum. Sample preparation was done using protein precipitation technique. Our method had a run time of 2.5 min and retention times of 1.6 min for all analytes. The standard curves were linear within the concentration range of 0.10 to 5.00 mg/L for levofloxacin and 0.10 to 4.99 mg/L for desmethyllevofloxacin; a correlation coefficient (R2) of 0.999 and 0.998 respectively. The lower limit of quantification for both analytes was 0.10 mg/L. Within-day precision ranged from 1.4% and 2.4% for levofloxacin, 1.5% to 5% for desmethyl-levofloxacin and between-day precision ranged from 3.6% to 4.1% for levofloxacin and 0.0% to 3.3% for desmethyl-levofloxacin; whereas, accuracy ranged from 0.1% to 12.7% for levofloxacin and 0.2% to 15.6% for desmethyl-levofloxacin. This method could be a useful asset for routine therapeutic drug monitoring of levofloxacin in multi-drug resistant tuberculosis patients.
{"title":"Determination of levofloxacin in human serum using liquid chromatography tandem mass spectrometry","authors":"S. Ghimire, K. V. Hateren, Natasha Vrubleuskaya, R. Koster, D. Touw, J. Alffenaar","doi":"10.17145/JAB.18.004","DOIUrl":"https://doi.org/10.17145/JAB.18.004","url":null,"abstract":"A rapid liquid chromatography tandem-mass spectrometry method was developed for the determination of levofloxacin and its metabolite (desmethyl-levofloxacin) in human serum. Sample preparation was done using protein precipitation technique. Our method had a run time of 2.5 min and retention times of 1.6 min for all analytes. The standard curves were linear within the concentration range of 0.10 to 5.00 mg/L for levofloxacin and 0.10 to 4.99 mg/L for desmethyllevofloxacin; a correlation coefficient (R2) of 0.999 and 0.998 respectively. The lower limit of quantification for both analytes was 0.10 mg/L. Within-day precision ranged from 1.4% and 2.4% for levofloxacin, 1.5% to 5% for desmethyl-levofloxacin and between-day precision ranged from 3.6% to 4.1% for levofloxacin and 0.0% to 3.3% for desmethyl-levofloxacin; whereas, accuracy ranged from 0.1% to 12.7% for levofloxacin and 0.2% to 15.6% for desmethyl-levofloxacin. This method could be a useful asset for routine therapeutic drug monitoring of levofloxacin in multi-drug resistant tuberculosis patients.","PeriodicalId":15014,"journal":{"name":"Journal of Applied Bioanalysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79807549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioanalysis. Just like last year, I like to start with taking the opportunity to wish all readers a Happy New Year and I hope that 2018 holds success and good fortune in any endeavor you pursue in the new year ahead of you. A special thank you is going out to all our authors, readers and reviewers, as well as to all the Editorial Board members for their continued support. In this article, I’ll take the opportunity to look back on the past year.
{"title":"Welcome to the fourth volume of the Journal of Applied Bioanalysis","authors":"R. Meesters","doi":"10.17145/JAB.18.001","DOIUrl":"https://doi.org/10.17145/JAB.18.001","url":null,"abstract":"Bioanalysis. Just like last year, I like to start with taking the opportunity to wish all readers a Happy New Year and I hope that 2018 holds success and good fortune in any endeavor you pursue in the new year ahead of you. A special thank you is going out to all our authors, readers and reviewers, as well as to all the Editorial Board members for their continued support. In this article, I’ll take the opportunity to look back on the past year.","PeriodicalId":15014,"journal":{"name":"Journal of Applied Bioanalysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77694274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Over the past two decades, three major trends have been observed in the bioanalysis world. • First, in liquid chromatography (LC) two-dimensional liquid chromatography (2D-LC) has emerged as one of the most active areas of technology advancement [1–3]. In 2D-LC, a conventional separation is carried out in the first dimension and aliquots of the effluent are collected and injected to a second-dimension column that has very different separation selectivity compared to the first-dimension column. Therefore, much higher peak capacity, and thus resolving power, can be achieved in 2D-LC compared to 1D-LC. This increased resolving power can be used to increase the likelihood of separating a complex mixture, or decrease the time required to fully separate simpler mixtures. In addition, 2D-LC allows the coupling of two completely different separation modes (e.g. reversed-phase and ionic exchange) in one method. This makes it possible to measure multiple attributes of a target analyte in one method instead of two separate methods. Although 2D-LC research has been going on for more than three decades, the speed of innovation and commercialization has accelerated in the last ten years due to efforts at both universities and instrument companies. • Second, Mass Spectrometry (MS) has become an indispensable tool in bioanalysis [4]. The ability of new MS instruments to more accurately characterize large molecules keeps improving. However, several challenges still remain. MS works best with volatile buffers of limited concentration. The ionization suppression effect still occurs when compounds with very different concentrations (e.g. several orders of magnitude) co-elute in chromatographic separations. These challenges to MS make LC separation a critical part of any bioanalysis workflow. • Finally, in the application area, biopharmaceutical research has become the fastest growing area in the pharmaceutical industry. In particular, monoclonal antibodies (mAbs) are currently the most important class of biotherapeutic molecules. As of 2016, seven of the top-ten-selling drugs were biologics, and six of these were mAb related [5]. In particular, the number one drug Humira (adalimumab) had an annual sales of $15.7 Billion dollars in 2016. Due to the large size of these antibodies at about 150 kDa molecular weight, analyzing them is very challenging. It often takes a suite of analytical tools to fully characterize the molecule and ensure good quality control of drug products involving these molecules. These three trends are developing at the same time and at high speed. It is our opinion that the combination of 2D-LC with MS is emerging as an exciting and essential tool for efficient, high quality biopharmaceutical analysis. In this article, we will discuss examples that demonstrate the power of 2D-LC-MS in this application area. JOURNAL OF APPLIED BIOANALYSIS, October 2017, p. 120-126. http://dx.doi.org/10.17145/jab.17.015 (ISSN 2405-710X) Vol. 3, No. 5
{"title":"The growing role of two-dimensional LC in the biopharmaceutical industry","authors":"Xiaoli Wang, Stephan M C Buckenmaier, D. Stoll","doi":"10.17145/JAB.17.015","DOIUrl":"https://doi.org/10.17145/JAB.17.015","url":null,"abstract":"Over the past two decades, three major trends have been observed in the bioanalysis world. • First, in liquid chromatography (LC) two-dimensional liquid chromatography (2D-LC) has emerged as one of the most active areas of technology advancement [1–3]. In 2D-LC, a conventional separation is carried out in the first dimension and aliquots of the effluent are collected and injected to a second-dimension column that has very different separation selectivity compared to the first-dimension column. Therefore, much higher peak capacity, and thus resolving power, can be achieved in 2D-LC compared to 1D-LC. This increased resolving power can be used to increase the likelihood of separating a complex mixture, or decrease the time required to fully separate simpler mixtures. In addition, 2D-LC allows the coupling of two completely different separation modes (e.g. reversed-phase and ionic exchange) in one method. This makes it possible to measure multiple attributes of a target analyte in one method instead of two separate methods. Although 2D-LC research has been going on for more than three decades, the speed of innovation and commercialization has accelerated in the last ten years due to efforts at both universities and instrument companies. • Second, Mass Spectrometry (MS) has become an indispensable tool in bioanalysis [4]. The ability of new MS instruments to more accurately characterize large molecules keeps improving. However, several challenges still remain. MS works best with volatile buffers of limited concentration. The ionization suppression effect still occurs when compounds with very different concentrations (e.g. several orders of magnitude) co-elute in chromatographic separations. These challenges to MS make LC separation a critical part of any bioanalysis workflow. • Finally, in the application area, biopharmaceutical research has become the fastest growing area in the pharmaceutical industry. In particular, monoclonal antibodies (mAbs) are currently the most important class of biotherapeutic molecules. As of 2016, seven of the top-ten-selling drugs were biologics, and six of these were mAb related [5]. In particular, the number one drug Humira (adalimumab) had an annual sales of $15.7 Billion dollars in 2016. Due to the large size of these antibodies at about 150 kDa molecular weight, analyzing them is very challenging. It often takes a suite of analytical tools to fully characterize the molecule and ensure good quality control of drug products involving these molecules. These three trends are developing at the same time and at high speed. It is our opinion that the combination of 2D-LC with MS is emerging as an exciting and essential tool for efficient, high quality biopharmaceutical analysis. In this article, we will discuss examples that demonstrate the power of 2D-LC-MS in this application area. JOURNAL OF APPLIED BIOANALYSIS, October 2017, p. 120-126. http://dx.doi.org/10.17145/jab.17.015 (ISSN 2405-710X) Vol. 3, No. 5","PeriodicalId":15014,"journal":{"name":"Journal of Applied Bioanalysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80915779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sequential immunoaffinity-LC/MS assay for quantitation of a therapeutic protein in monkey plasma","authors":"Lin-Zhi Chen, D. Roos, E. Philip, S. Pagels","doi":"10.17145/JAB.17.016","DOIUrl":"https://doi.org/10.17145/JAB.17.016","url":null,"abstract":"","PeriodicalId":15014,"journal":{"name":"Journal of Applied Bioanalysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74841392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Georgia Dimitropoulou, Sophia Karastogianni, S. Girousi
{"title":"Development of an electrochemical DNA biosensor for the detection of vitamin B12 (cyanocobalamin) at a carbon paste modified electrode with a manganese(II) complex","authors":"Georgia Dimitropoulou, Sophia Karastogianni, S. Girousi","doi":"10.17145/JAB.17.011","DOIUrl":"https://doi.org/10.17145/JAB.17.011","url":null,"abstract":"","PeriodicalId":15014,"journal":{"name":"Journal of Applied Bioanalysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88261058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The data reported in literature demonstrate that carbon paste electrodes (CPEs) are very suitable for a variety of applications and many works have thus been devoted in the development of new sensitive and selective electrode surfaces based on carbon paste as the electrode material of choice. The application of novel and promising carbonaceous materials, as electrode surfaces, is an issue of great concern. In this work the experimental results of the characterization and comparison of electrode surfaces based on alternatively prepared carbonaceous materials (activated carbon (B), HNO3 oxidized activated carbon (B5), Ag impregnated activated carbon (B-Ag) and graphite oxide (GO), are being demonstrated. Scaning Electron Microscopy SEM), surface acidity, FTIR spectroscopy, XRD diffractometry and electrochemical techniques (cyclic voltammetry, differential pulse voltammetry) were applied in the characterization of novel carbonaceous materials aimed at electrochemical DNA sensing.
{"title":"Application of promising carbonaceous materials in electrochemical DNA sensing","authors":"Sophia Karastogianni, E. Deliyanni, S. Girousi","doi":"10.17145/jab.17.014","DOIUrl":"https://doi.org/10.17145/jab.17.014","url":null,"abstract":"The data reported in literature demonstrate that carbon paste electrodes (CPEs) are very suitable for a variety of applications and many works have thus been devoted in the development of new sensitive and selective electrode surfaces based on carbon paste as the electrode material of choice. The application of novel and promising carbonaceous materials, as electrode surfaces, is an issue of great concern. In this work the experimental results of the characterization and comparison of electrode surfaces based on alternatively prepared carbonaceous materials (activated carbon (B), HNO3 oxidized activated carbon (B5), Ag impregnated activated carbon (B-Ag) and graphite oxide (GO), are being demonstrated. Scaning Electron Microscopy SEM), surface acidity, FTIR spectroscopy, XRD diffractometry and electrochemical techniques (cyclic voltammetry, differential pulse voltammetry) were applied in the characterization of novel carbonaceous materials aimed at electrochemical DNA sensing.","PeriodicalId":15014,"journal":{"name":"Journal of Applied Bioanalysis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84451229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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