Quantitation of cytidine-5'-monophospho-N-acetylneuraminic acid in human leukocytes using LC-MS/MS: method development and validation.


Journal

Biomedical chromatography : BMC
ISSN: 1099-0801
Titre abrégé: Biomed Chromatogr
Pays: England
ID NLM: 8610241

Informations de publication

Date de publication:
Feb 2020
Historique:
received: 26 08 2019
revised: 18 10 2019
accepted: 21 10 2019
pubmed: 7 11 2019
medline: 26 2 2020
entrez: 7 11 2019
Statut: ppublish

Résumé

The biosynthesis of sialic acid (Neu5Ac) leads to the intracellular production of cytidine-5'-monophospho-N-acetylneuraminic acid (CMP-Neu5Ac), the active sialic acid donor to nascent glycans (glycoproteins and glycolipids) in the Golgi. UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase myopathy is a rare autosomal recessive muscular disease characterized by progressive muscle weakness and atrophy. To quantify the intracellular levels of CMP-Neu5Ac as well as N-acetylmannosamine (ManNAc) and Neu5Ac in human leukocytes, we developed and validated robust liquid chromatography-tandem mass spectrometry methods. A fit-for-purpose approach was implemented for method validation. Hydrophilic interaction chromatography was used to retain three hydrophilic analytes. The human leukocyte pellets were lysed and extracted in a methanol-water mixture and the leukocyte extract was used for LC-MS/MS analysis. The lower limits of quantitation for ManNAc, Neu5Ac and CMP-Neu5Ac were 25.0, 25.0 and 10.0 ng/ml, respectively. These validated methods were applied to a clinical study.

Identifiants

pubmed: 31691999
doi: 10.1002/bmc.4735
pmc: PMC8336284
mid: NIHMS1728435
doi:

Substances chimiques

Sialic Acids 0
cytidine-5'-monophosphosialic acid 0
Cytidine Monophosphate F469818O25

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e4735

Subventions

Organisme : Intramural NIH HHS
ID : Z01 HG000215
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIB TR000002
Pays : United States
Organisme : NCATS NIH HHS
Pays : United States
Organisme : NHGRI NIH HHS
Pays : United States

Informations de copyright

© 2019 John Wiley & Sons, Ltd.

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Auteurs

Meng Fang (M)

Alliance Pharma, 17 Lee Boulevard, Malvern, PA, USA.

Xin Xu (X)

Therapeutic Development Branch, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.

Michael Zhang (M)

Alliance Pharma, 17 Lee Boulevard, Malvern, PA, USA.

Yifan Shi (Y)

Alliance Pharma, 17 Lee Boulevard, Malvern, PA, USA.

Guodong Gu (G)

Alliance Pharma, 17 Lee Boulevard, Malvern, PA, USA.

Wanjing Liu (W)

Alliance Pharma, 17 Lee Boulevard, Malvern, PA, USA.

Bradley Class (B)

Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD, USA.

Carla Ciccone (C)

Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD, USA.

William A Gahl (WA)

Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD, USA.

Marjan Huizing (M)

Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD, USA.

Nuria Carrillo (N)

Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD, USA.

Amy Q Wang (AQ)

Therapeutic Development Branch, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.

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Classifications MeSH