Simultaneous LC-MS/MS determination of phenylbutyrate, phenylacetate benzoate and their corresponding metabolites phenylacetylglutamine and hippurate in blood and urine
Inborn errors of urea metabolism result in hyperammonemia. Treatment of urea cycle disorders can effectively lower plasma ammonium levels and results in survival in the majority of patients. Available medications for treating urea cycle disorders include sodium benzoate (BA), sodium phenylacetate (P...
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| Veröffentlicht in: | Journal of inherited metabolic disease 2010-12, Vol.33 (Suppl 3), p.321-328 |
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| creator | Laryea, Maurice D. Herebian, Diran Meissner, Thomas Mayatepek, Ertan |
| description | Inborn errors of urea metabolism result in hyperammonemia. Treatment of urea cycle disorders can effectively lower plasma ammonium levels and results in survival in the majority of patients. Available medications for treating urea cycle disorders include sodium benzoate (BA), sodium phenylacetate (PAA), and sodium phenylbutyrate (PBA) and are given to provide alternate routes for disposition of waste nitrogen excretion. In this study, we develop and validate a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of benzoic acid, phenylacetic acid, phenylbutyric acid, phenylacetylglutamine, and hippuric acid in plasma and urine from children with inborn errors of urea synthesis. Plasma extracts and diluted urine samples were injected on a reverse-phase column and identified and quantified by selected reaction monitoring (SRM) in negative ion mode. Deuterated analogues served as internal standards. Analysis time was 7 min. Assay precision, accuracy, and linearity and sample stability were determined using enriched samples. Quantification limits of the method were 100 ng/ml (0.3–0.8 μmol/L) for all analytes, and recoveries were >90%. Inter- and intraday relative standard deviations were |
| doi_str_mv | 10.1007/s10545-010-9172-9 |
| format | Article |
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Treatment of urea cycle disorders can effectively lower plasma ammonium levels and results in survival in the majority of patients. Available medications for treating urea cycle disorders include sodium benzoate (BA), sodium phenylacetate (PAA), and sodium phenylbutyrate (PBA) and are given to provide alternate routes for disposition of waste nitrogen excretion. In this study, we develop and validate a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of benzoic acid, phenylacetic acid, phenylbutyric acid, phenylacetylglutamine, and hippuric acid in plasma and urine from children with inborn errors of urea synthesis. Plasma extracts and diluted urine samples were injected on a reverse-phase column and identified and quantified by selected reaction monitoring (SRM) in negative ion mode. Deuterated analogues served as internal standards. Analysis time was 7 min. Assay precision, accuracy, and linearity and sample stability were determined using enriched samples. Quantification limits of the method were 100 ng/ml (0.3–0.8 μmol/L) for all analytes, and recoveries were >90%. Inter- and intraday relative standard deviations were <10%. Our newly developed LC-MS/MS represents a robust, sensitive, and rapid method that allows simultaneous determination of the five compounds in plasma and urine.</description><identifier>ISSN: 1573-2665</identifier><identifier>ISSN: 0141-8955</identifier><identifier>EISSN: 1573-2665</identifier><identifier>DOI: 10.1007/s10545-010-9172-9</identifier><identifier>PMID: 20694517</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Benzoates - blood ; Benzoates - therapeutic use ; Benzoates - urine ; Biochemistry ; Biomarkers - blood ; Biomarkers - urine ; Biotransformation ; Calibration ; Chromatography, Reverse-Phase - standards ; Glutamine - analogs & derivatives ; Glutamine - blood ; Glutamine - urine ; Hippurates - blood ; Hippurates - urine ; Human Genetics ; Humans ; Hyperammonemia - blood ; Hyperammonemia - drug therapy ; Hyperammonemia - urine ; Internal Medicine ; Limit of Detection ; Linear Models ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Pediatrics ; Phenylacetates - blood ; Phenylacetates - therapeutic use ; Phenylacetates - urine ; Phenylbutyrates - blood ; Phenylbutyrates - therapeutic use ; Phenylbutyrates - urine ; Predictive Value of Tests ; Reference Standards ; Reproducibility of Results ; Research Report ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry - standards ; Urea Cycle Disorders, Inborn - blood ; Urea Cycle Disorders, Inborn - drug therapy ; Urea Cycle Disorders, Inborn - urine</subject><ispartof>Journal of inherited metabolic disease, 2010-12, Vol.33 (Suppl 3), p.321-328</ispartof><rights>SSIEM and Springer 2010</rights><rights>2010 SSIEM</rights><rights>SSIEM and Springer Science+Business Media Dordrecht 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4631-51a2f1a2eaee33db9a8d1e380be1a31d2b6b85ea5a5d8bb5fcd3c733b961e023</citedby><cites>FETCH-LOGICAL-c4631-51a2f1a2eaee33db9a8d1e380be1a31d2b6b85ea5a5d8bb5fcd3c733b961e023</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10545-010-9172-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10545-010-9172-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,1416,27915,27916,41479,42548,45565,45566,51310</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20694517$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Laryea, Maurice D.</creatorcontrib><creatorcontrib>Herebian, Diran</creatorcontrib><creatorcontrib>Meissner, Thomas</creatorcontrib><creatorcontrib>Mayatepek, Ertan</creatorcontrib><title>Simultaneous LC-MS/MS determination of phenylbutyrate, phenylacetate benzoate and their corresponding metabolites phenylacetylglutamine and hippurate in blood and urine</title><title>Journal of inherited metabolic disease</title><addtitle>J Inherit Metab Dis</addtitle><addtitle>J Inherit Metab Dis</addtitle><description>Inborn errors of urea metabolism result in hyperammonemia. Treatment of urea cycle disorders can effectively lower plasma ammonium levels and results in survival in the majority of patients. Available medications for treating urea cycle disorders include sodium benzoate (BA), sodium phenylacetate (PAA), and sodium phenylbutyrate (PBA) and are given to provide alternate routes for disposition of waste nitrogen excretion. In this study, we develop and validate a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of benzoic acid, phenylacetic acid, phenylbutyric acid, phenylacetylglutamine, and hippuric acid in plasma and urine from children with inborn errors of urea synthesis. Plasma extracts and diluted urine samples were injected on a reverse-phase column and identified and quantified by selected reaction monitoring (SRM) in negative ion mode. Deuterated analogues served as internal standards. Analysis time was 7 min. Assay precision, accuracy, and linearity and sample stability were determined using enriched samples. Quantification limits of the method were 100 ng/ml (0.3–0.8 μmol/L) for all analytes, and recoveries were >90%. Inter- and intraday relative standard deviations were <10%. Our newly developed LC-MS/MS represents a robust, sensitive, and rapid method that allows simultaneous determination of the five compounds in plasma and urine.</description><subject>Benzoates - blood</subject><subject>Benzoates - therapeutic use</subject><subject>Benzoates - urine</subject><subject>Biochemistry</subject><subject>Biomarkers - blood</subject><subject>Biomarkers - urine</subject><subject>Biotransformation</subject><subject>Calibration</subject><subject>Chromatography, Reverse-Phase - standards</subject><subject>Glutamine - analogs & derivatives</subject><subject>Glutamine - blood</subject><subject>Glutamine - urine</subject><subject>Hippurates - blood</subject><subject>Hippurates - urine</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Hyperammonemia - blood</subject><subject>Hyperammonemia - drug therapy</subject><subject>Hyperammonemia - urine</subject><subject>Internal Medicine</subject><subject>Limit of Detection</subject><subject>Linear Models</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Pediatrics</subject><subject>Phenylacetates - blood</subject><subject>Phenylacetates - therapeutic use</subject><subject>Phenylacetates - urine</subject><subject>Phenylbutyrates - blood</subject><subject>Phenylbutyrates - therapeutic use</subject><subject>Phenylbutyrates - urine</subject><subject>Predictive Value of Tests</subject><subject>Reference Standards</subject><subject>Reproducibility of Results</subject><subject>Research Report</subject><subject>Spectrometry, Mass, Electrospray Ionization</subject><subject>Tandem Mass Spectrometry - standards</subject><subject>Urea Cycle Disorders, Inborn - blood</subject><subject>Urea Cycle Disorders, Inborn - drug therapy</subject><subject>Urea Cycle Disorders, Inborn - urine</subject><issn>1573-2665</issn><issn>0141-8955</issn><issn>1573-2665</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqFkctuFDEQRVsIRELCB7BBltjSxI9xP5ZoeCWaURaTvWW3q2ccdduNH0LNF_GZeOgBzSZiYbmqdM-tkm5RvCH4A8G4vgkE8xUvMcFlS2pats-KS8JrVtKq4s_P6oviVQiPGOO24fxlcUFx1a44qS-LXzszpiFKCy4FtFmX293Ndoc0RPCjsTIaZ5Hr0XQAOw8qxdnLCO9Pvewg5hYpsD_dsZBWo3gA41HnvIcwOauN3aMx65QbTIRwhs7DfkhR5j0LeTDTlI7-yFikBuf0n3HyWXBdvOjlEOD16b8qHr58flh_Kzf3X2_XHzdlt6oYKTmRtM8PJABjWrWy0QRYgxUQyYimqlINB8kl141SvO8062rGVFsRwJRdFe8W28m77wlCFI8ueZs3CrKqSM1ZS5usIouq8y4ED72YvBmlnwXB4hiNWKIRORpxjEa0mXl7ck5qBP2P-JtFFtSL4IcZYP6_o7i73X7CjJJM0oUMGbJ78GdHP3nPb71Mryk</recordid><startdate>201012</startdate><enddate>201012</enddate><creator>Laryea, Maurice D.</creator><creator>Herebian, Diran</creator><creator>Meissner, Thomas</creator><creator>Mayatepek, Ertan</creator><general>Springer Netherlands</general><general>Blackwell Publishing Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope></search><sort><creationdate>201012</creationdate><title>Simultaneous LC-MS/MS determination of phenylbutyrate, phenylacetate benzoate and their corresponding metabolites phenylacetylglutamine and hippurate in blood and urine</title><author>Laryea, Maurice D. ; Herebian, Diran ; Meissner, Thomas ; Mayatepek, Ertan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4631-51a2f1a2eaee33db9a8d1e380be1a31d2b6b85ea5a5d8bb5fcd3c733b961e023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Benzoates - blood</topic><topic>Benzoates - therapeutic use</topic><topic>Benzoates - urine</topic><topic>Biochemistry</topic><topic>Biomarkers - blood</topic><topic>Biomarkers - urine</topic><topic>Biotransformation</topic><topic>Calibration</topic><topic>Chromatography, Reverse-Phase - standards</topic><topic>Glutamine - analogs & derivatives</topic><topic>Glutamine - blood</topic><topic>Glutamine - urine</topic><topic>Hippurates - blood</topic><topic>Hippurates - urine</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Hyperammonemia - blood</topic><topic>Hyperammonemia - drug therapy</topic><topic>Hyperammonemia - urine</topic><topic>Internal Medicine</topic><topic>Limit of Detection</topic><topic>Linear Models</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic Diseases</topic><topic>Pediatrics</topic><topic>Phenylacetates - blood</topic><topic>Phenylacetates - therapeutic use</topic><topic>Phenylacetates - urine</topic><topic>Phenylbutyrates - blood</topic><topic>Phenylbutyrates - therapeutic use</topic><topic>Phenylbutyrates - urine</topic><topic>Predictive Value of Tests</topic><topic>Reference Standards</topic><topic>Reproducibility of Results</topic><topic>Research Report</topic><topic>Spectrometry, Mass, Electrospray Ionization</topic><topic>Tandem Mass Spectrometry - standards</topic><topic>Urea Cycle Disorders, Inborn - blood</topic><topic>Urea Cycle Disorders, Inborn - drug therapy</topic><topic>Urea Cycle Disorders, Inborn - urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Laryea, Maurice D.</creatorcontrib><creatorcontrib>Herebian, Diran</creatorcontrib><creatorcontrib>Meissner, Thomas</creatorcontrib><creatorcontrib>Mayatepek, Ertan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><jtitle>Journal of inherited metabolic disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Laryea, Maurice D.</au><au>Herebian, Diran</au><au>Meissner, Thomas</au><au>Mayatepek, Ertan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Simultaneous LC-MS/MS determination of phenylbutyrate, phenylacetate benzoate and their corresponding metabolites phenylacetylglutamine and hippurate in blood and urine</atitle><jtitle>Journal of inherited metabolic disease</jtitle><stitle>J Inherit Metab Dis</stitle><addtitle>J Inherit Metab Dis</addtitle><date>2010-12</date><risdate>2010</risdate><volume>33</volume><issue>Suppl 3</issue><spage>321</spage><epage>328</epage><pages>321-328</pages><issn>1573-2665</issn><issn>0141-8955</issn><eissn>1573-2665</eissn><abstract>Inborn errors of urea metabolism result in hyperammonemia. Treatment of urea cycle disorders can effectively lower plasma ammonium levels and results in survival in the majority of patients. Available medications for treating urea cycle disorders include sodium benzoate (BA), sodium phenylacetate (PAA), and sodium phenylbutyrate (PBA) and are given to provide alternate routes for disposition of waste nitrogen excretion. In this study, we develop and validate a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of benzoic acid, phenylacetic acid, phenylbutyric acid, phenylacetylglutamine, and hippuric acid in plasma and urine from children with inborn errors of urea synthesis. Plasma extracts and diluted urine samples were injected on a reverse-phase column and identified and quantified by selected reaction monitoring (SRM) in negative ion mode. Deuterated analogues served as internal standards. Analysis time was 7 min. Assay precision, accuracy, and linearity and sample stability were determined using enriched samples. Quantification limits of the method were 100 ng/ml (0.3–0.8 μmol/L) for all analytes, and recoveries were >90%. Inter- and intraday relative standard deviations were <10%. Our newly developed LC-MS/MS represents a robust, sensitive, and rapid method that allows simultaneous determination of the five compounds in plasma and urine.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>20694517</pmid><doi>10.1007/s10545-010-9172-9</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1573-2665 |
| ispartof | Journal of inherited metabolic disease, 2010-12, Vol.33 (Suppl 3), p.321-328 |
| issn | 1573-2665 0141-8955 1573-2665 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Springer Nature - Complete Springer Journals |
| subjects | Benzoates - blood Benzoates - therapeutic use Benzoates - urine Biochemistry Biomarkers - blood Biomarkers - urine Biotransformation Calibration Chromatography, Reverse-Phase - standards Glutamine - analogs & derivatives Glutamine - blood Glutamine - urine Hippurates - blood Hippurates - urine Human Genetics Humans Hyperammonemia - blood Hyperammonemia - drug therapy Hyperammonemia - urine Internal Medicine Limit of Detection Linear Models Medicine Medicine & Public Health Metabolic Diseases Pediatrics Phenylacetates - blood Phenylacetates - therapeutic use Phenylacetates - urine Phenylbutyrates - blood Phenylbutyrates - therapeutic use Phenylbutyrates - urine Predictive Value of Tests Reference Standards Reproducibility of Results Research Report Spectrometry, Mass, Electrospray Ionization Tandem Mass Spectrometry - standards Urea Cycle Disorders, Inborn - blood Urea Cycle Disorders, Inborn - drug therapy Urea Cycle Disorders, Inborn - urine |
| title | Simultaneous LC-MS/MS determination of phenylbutyrate, phenylacetate benzoate and their corresponding metabolites phenylacetylglutamine and hippurate in blood and urine |
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