A simple and fast liquid chromatography–tandem mass spectrometry method for measurement of underivatized l-arginine, symmetric dimethylarginine, and asymmetric dimethylarginine and establishment of the reference ranges

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and an established biomarker for endothelial function, while symmetric dimethylarginine (SDMA), an emerging biomarker for renal function, has been shown to outperform creatinine-based equations for estimated glome...

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Main Author: El-Khoury, Joe (author)
Other Authors: Bunch, Dustin (author), Reineks, Edmunds (author), Jackson, Raymond (author), Steinle, Roxanne (author), Wang, Sihe (author)
Format: article
Published: 2012
Online Access:http://hdl.handle.net/10725/4024
http://dx.doi.org/10.1007/s00216-011-5462-9
http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php
http://link.springer.com/article/10.1007/s00216-011-5462-9
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author El-Khoury, Joe
author2 Bunch, Dustin
Reineks, Edmunds
Jackson, Raymond
Steinle, Roxanne
Wang, Sihe
author2_role author
author
author
author
author
author_facet El-Khoury, Joe
Bunch, Dustin
Reineks, Edmunds
Jackson, Raymond
Steinle, Roxanne
Wang, Sihe
author_role author
dc.creator.none.fl_str_mv El-Khoury, Joe
Bunch, Dustin
Reineks, Edmunds
Jackson, Raymond
Steinle, Roxanne
Wang, Sihe
dc.date.none.fl_str_mv 2012
2016-06-14T07:07:13Z
2016-06-14T07:07:13Z
2016-06-14
dc.identifier.none.fl_str_mv 1618-2642
http://hdl.handle.net/10725/4024
http://dx.doi.org/10.1007/s00216-011-5462-9
El-Khoury, J. M., Bunch, D. R., Reineks, E., Jackson, R., Steinle, R., & Wang, S. (2012). A simple and fast liquid chromatography–tandem mass spectrometry method for measurement of underivatized l-arginine, symmetric dimethylarginine, and asymmetric dimethylarginine and establishment of the reference ranges. Analytical and bioanalytical chemistry, 402(2), 771-779.
http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php
http://link.springer.com/article/10.1007/s00216-011-5462-9
dc.language.none.fl_str_mv en
dc.relation.none.fl_str_mv Analytical and Bioanalytical Chemistry
dc.rights.*.fl_str_mv info:eu-repo/semantics/openAccess
dc.title.none.fl_str_mv A simple and fast liquid chromatography–tandem mass spectrometry method for measurement of underivatized l-arginine, symmetric dimethylarginine, and asymmetric dimethylarginine and establishment of the reference ranges
dc.type.none.fl_str_mv Article
info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/article
description Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and an established biomarker for endothelial function, while symmetric dimethylarginine (SDMA), an emerging biomarker for renal function, has been shown to outperform creatinine-based equations for estimated glomerular filtration rate. In order to study these analytes for clinical research, a fast and simple method for measuring arginine (ARG), SDMA, and ADMA in plasma by liquid chromatography–tandem mass spectrometry (LC-MS/MS) has been developed. Plasma (50 μL) was mixed with 50 μL of internal standard of 13C-arginine and d7-ADMA followed by protein precipitation with methanol containing 1% ammonium acetate (300 μL). After centrifugation, the supernatant (100 μL) was mixed with 300 μL of acetonitrile with 1% formic acid, and the mixture was injected onto a silica column monitored by a mass spectrometer. The analytical cycle time was 5.0 min. The method was linear from 5.7 to 489.7 μM for ARG, 0.06 to 5.15 μM for SDMA, and from 0.34 to 5.65 μM for ADMA, with an accuracy of 99.0–120.0%. Total coefficients of variation for all analytes ranged from 2.7% to 7.7% for three concentration levels. The effects of hemolysis, lipemia, uremia, icterus, specimen tube types, storage at different temperature, and freeze/thaw were thoroughly investigated. Reference ranges were established using 51 well-defined reference subjects (12 men and 39 women, age 19–64 years): 53.1–129.7 μM for ARG, 0.32–0.65 μM for SDMA, and 0.36–0.67 μM for ADMA. In conclusion, the validated LC-MS/MS method described here offers a fast and reliable ARG, SDMA, and ADMA quantitation in plasma with minimum sample preparation.
eu_rights_str_mv openAccess
format article
id LAURepo_21b46e1857ff7dd54c558b5c6263dcd6
identifier_str_mv 1618-2642
El-Khoury, J. M., Bunch, D. R., Reineks, E., Jackson, R., Steinle, R., & Wang, S. (2012). A simple and fast liquid chromatography–tandem mass spectrometry method for measurement of underivatized l-arginine, symmetric dimethylarginine, and asymmetric dimethylarginine and establishment of the reference ranges. Analytical and bioanalytical chemistry, 402(2), 771-779.
language_invalid_str_mv en
network_acronym_str LAURepo
network_name_str Lebanese American University repository
oai_identifier_str oai:laur.lau.edu.lb:10725/4024
publishDate 2012
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spelling A simple and fast liquid chromatography–tandem mass spectrometry method for measurement of underivatized l-arginine, symmetric dimethylarginine, and asymmetric dimethylarginine and establishment of the reference rangesEl-Khoury, JoeBunch, DustinReineks, EdmundsJackson, RaymondSteinle, RoxanneWang, SiheAsymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and an established biomarker for endothelial function, while symmetric dimethylarginine (SDMA), an emerging biomarker for renal function, has been shown to outperform creatinine-based equations for estimated glomerular filtration rate. In order to study these analytes for clinical research, a fast and simple method for measuring arginine (ARG), SDMA, and ADMA in plasma by liquid chromatography–tandem mass spectrometry (LC-MS/MS) has been developed. Plasma (50 μL) was mixed with 50 μL of internal standard of 13C-arginine and d7-ADMA followed by protein precipitation with methanol containing 1% ammonium acetate (300 μL). After centrifugation, the supernatant (100 μL) was mixed with 300 μL of acetonitrile with 1% formic acid, and the mixture was injected onto a silica column monitored by a mass spectrometer. The analytical cycle time was 5.0 min. The method was linear from 5.7 to 489.7 μM for ARG, 0.06 to 5.15 μM for SDMA, and from 0.34 to 5.65 μM for ADMA, with an accuracy of 99.0–120.0%. Total coefficients of variation for all analytes ranged from 2.7% to 7.7% for three concentration levels. The effects of hemolysis, lipemia, uremia, icterus, specimen tube types, storage at different temperature, and freeze/thaw were thoroughly investigated. Reference ranges were established using 51 well-defined reference subjects (12 men and 39 women, age 19–64 years): 53.1–129.7 μM for ARG, 0.32–0.65 μM for SDMA, and 0.36–0.67 μM for ADMA. In conclusion, the validated LC-MS/MS method described here offers a fast and reliable ARG, SDMA, and ADMA quantitation in plasma with minimum sample preparation.PublishedN/A2016-06-14T07:07:13Z2016-06-14T07:07:13Z20122016-06-14Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1618-2642http://hdl.handle.net/10725/4024http://dx.doi.org/10.1007/s00216-011-5462-9El-Khoury, J. M., Bunch, D. R., Reineks, E., Jackson, R., Steinle, R., & Wang, S. (2012). A simple and fast liquid chromatography–tandem mass spectrometry method for measurement of underivatized l-arginine, symmetric dimethylarginine, and asymmetric dimethylarginine and establishment of the reference ranges. Analytical and bioanalytical chemistry, 402(2), 771-779.http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.phphttp://link.springer.com/article/10.1007/s00216-011-5462-9enAnalytical and Bioanalytical Chemistryinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/40242021-03-19T10:00:52Z
spellingShingle A simple and fast liquid chromatography–tandem mass spectrometry method for measurement of underivatized l-arginine, symmetric dimethylarginine, and asymmetric dimethylarginine and establishment of the reference ranges
El-Khoury, Joe
status_str publishedVersion
title A simple and fast liquid chromatography–tandem mass spectrometry method for measurement of underivatized l-arginine, symmetric dimethylarginine, and asymmetric dimethylarginine and establishment of the reference ranges
title_full A simple and fast liquid chromatography–tandem mass spectrometry method for measurement of underivatized l-arginine, symmetric dimethylarginine, and asymmetric dimethylarginine and establishment of the reference ranges
title_fullStr A simple and fast liquid chromatography–tandem mass spectrometry method for measurement of underivatized l-arginine, symmetric dimethylarginine, and asymmetric dimethylarginine and establishment of the reference ranges
title_full_unstemmed A simple and fast liquid chromatography–tandem mass spectrometry method for measurement of underivatized l-arginine, symmetric dimethylarginine, and asymmetric dimethylarginine and establishment of the reference ranges
title_short A simple and fast liquid chromatography–tandem mass spectrometry method for measurement of underivatized l-arginine, symmetric dimethylarginine, and asymmetric dimethylarginine and establishment of the reference ranges
title_sort A simple and fast liquid chromatography–tandem mass spectrometry method for measurement of underivatized l-arginine, symmetric dimethylarginine, and asymmetric dimethylarginine and establishment of the reference ranges
url http://hdl.handle.net/10725/4024
http://dx.doi.org/10.1007/s00216-011-5462-9
http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php
http://link.springer.com/article/10.1007/s00216-011-5462-9