A new LC-MS assay for the quantitative analysis of vitamin K metabolites in human urine[S]
Vitamin K (VK), in both its phylloquinone and menaquinone forms, has been hypothesized to undergo ω- and β-oxidation on its hydrophobic side chain in order to generate the observed urinary metabolites, K acid I and K acid II, which are excreted primarily as glucuronide conjugates. Synthetic standard...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2019-04-01
|
Series: | Journal of Lipid Research |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520326018 |
id |
doaj-f76ce9485fad4bcdba19644badf8ed00 |
---|---|
record_format |
Article |
spelling |
doaj-f76ce9485fad4bcdba19644badf8ed002021-04-29T04:35:46ZengElsevierJournal of Lipid Research0022-22752019-04-01604892899A new LC-MS assay for the quantitative analysis of vitamin K metabolites in human urine[S]Matthew G. McDonald0Catherine K. Yeung1Aaron M. Teitelbaum2Amanda L. Johnson3Shinya Fujii4Hiroyuki Kagechika5Allan E. Rettie6To whom correspondence should be addressed; Departments of Medicinal Chemistry University of Washington, Seattle, WA 98195-7610; To whom correspondence should be addressedDepartments of Pharmacy, University of Washington, Seattle, WA 98195-7610Departments of Medicinal Chemistry University of Washington, Seattle, WA 98195-7610Departments of Medicinal Chemistry University of Washington, Seattle, WA 98195-7610Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo 101-0062, JapanInstitute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo 101-0062, JapanDepartments of Medicinal Chemistry University of Washington, Seattle, WA 98195-7610Vitamin K (VK), in both its phylloquinone and menaquinone forms, has been hypothesized to undergo ω- and β-oxidation on its hydrophobic side chain in order to generate the observed urinary metabolites, K acid I and K acid II, which are excreted primarily as glucuronide conjugates. Synthetic standards of K acid I, K acid II, and a putative intermediate metabolite, menaquinone (MK)1 ω-COOH, were used to develop and optimize a new atmospheric pressure negative chemical ionization LC-MS/MS assay for the quantitation of these compounds in urine from untreated individuals and subjects treated with a high dose VK supplement. VK catabolites were extracted from urine, deconjugated, and converted to their methyl ester derivatives using previously reported methodology. The assay showed a high degree of sensitivity, with limits of detection below 10–50 fmol of metabolite per milliliter of urine, as well as an inter-assay precision of 8–12%. Metabolite standards provided unambiguous evidence for MK1 ω-COOH as a new human urinary metabolite of VK. This assay provides a minimally invasive, highly sensitive, and specific alternative for monitoring VK status in humans.http://www.sciencedirect.com/science/article/pii/S0022227520326018beta-oxidationomega-oxidationliquid chromatography-mass spectrometrymenaquinonephylloquinone |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Matthew G. McDonald Catherine K. Yeung Aaron M. Teitelbaum Amanda L. Johnson Shinya Fujii Hiroyuki Kagechika Allan E. Rettie |
spellingShingle |
Matthew G. McDonald Catherine K. Yeung Aaron M. Teitelbaum Amanda L. Johnson Shinya Fujii Hiroyuki Kagechika Allan E. Rettie A new LC-MS assay for the quantitative analysis of vitamin K metabolites in human urine[S] Journal of Lipid Research beta-oxidation omega-oxidation liquid chromatography-mass spectrometry menaquinone phylloquinone |
author_facet |
Matthew G. McDonald Catherine K. Yeung Aaron M. Teitelbaum Amanda L. Johnson Shinya Fujii Hiroyuki Kagechika Allan E. Rettie |
author_sort |
Matthew G. McDonald |
title |
A new LC-MS assay for the quantitative analysis of vitamin K metabolites in human urine[S] |
title_short |
A new LC-MS assay for the quantitative analysis of vitamin K metabolites in human urine[S] |
title_full |
A new LC-MS assay for the quantitative analysis of vitamin K metabolites in human urine[S] |
title_fullStr |
A new LC-MS assay for the quantitative analysis of vitamin K metabolites in human urine[S] |
title_full_unstemmed |
A new LC-MS assay for the quantitative analysis of vitamin K metabolites in human urine[S] |
title_sort |
new lc-ms assay for the quantitative analysis of vitamin k metabolites in human urine[s] |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2019-04-01 |
description |
Vitamin K (VK), in both its phylloquinone and menaquinone forms, has been hypothesized to undergo ω- and β-oxidation on its hydrophobic side chain in order to generate the observed urinary metabolites, K acid I and K acid II, which are excreted primarily as glucuronide conjugates. Synthetic standards of K acid I, K acid II, and a putative intermediate metabolite, menaquinone (MK)1 ω-COOH, were used to develop and optimize a new atmospheric pressure negative chemical ionization LC-MS/MS assay for the quantitation of these compounds in urine from untreated individuals and subjects treated with a high dose VK supplement. VK catabolites were extracted from urine, deconjugated, and converted to their methyl ester derivatives using previously reported methodology. The assay showed a high degree of sensitivity, with limits of detection below 10–50 fmol of metabolite per milliliter of urine, as well as an inter-assay precision of 8–12%. Metabolite standards provided unambiguous evidence for MK1 ω-COOH as a new human urinary metabolite of VK. This assay provides a minimally invasive, highly sensitive, and specific alternative for monitoring VK status in humans. |
topic |
beta-oxidation omega-oxidation liquid chromatography-mass spectrometry menaquinone phylloquinone |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520326018 |
work_keys_str_mv |
AT matthewgmcdonald anewlcmsassayforthequantitativeanalysisofvitaminkmetabolitesinhumanurines AT catherinekyeung anewlcmsassayforthequantitativeanalysisofvitaminkmetabolitesinhumanurines AT aaronmteitelbaum anewlcmsassayforthequantitativeanalysisofvitaminkmetabolitesinhumanurines AT amandaljohnson anewlcmsassayforthequantitativeanalysisofvitaminkmetabolitesinhumanurines AT shinyafujii anewlcmsassayforthequantitativeanalysisofvitaminkmetabolitesinhumanurines AT hiroyukikagechika anewlcmsassayforthequantitativeanalysisofvitaminkmetabolitesinhumanurines AT allanerettie anewlcmsassayforthequantitativeanalysisofvitaminkmetabolitesinhumanurines AT matthewgmcdonald newlcmsassayforthequantitativeanalysisofvitaminkmetabolitesinhumanurines AT catherinekyeung newlcmsassayforthequantitativeanalysisofvitaminkmetabolitesinhumanurines AT aaronmteitelbaum newlcmsassayforthequantitativeanalysisofvitaminkmetabolitesinhumanurines AT amandaljohnson newlcmsassayforthequantitativeanalysisofvitaminkmetabolitesinhumanurines AT shinyafujii newlcmsassayforthequantitativeanalysisofvitaminkmetabolitesinhumanurines AT hiroyukikagechika newlcmsassayforthequantitativeanalysisofvitaminkmetabolitesinhumanurines AT allanerettie newlcmsassayforthequantitativeanalysisofvitaminkmetabolitesinhumanurines |
_version_ |
1721502441021636608 |