Document Detail


Two mass-spectrometric techniques for quantifying serine enantiomers and glycine in cerebrospinal fluid: potential confounders and age-dependent ranges.
MedLine Citation:
PMID:  18606633     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The recent discovery and specific functions of D-amino acids in humans are bound to lead to the revelation of D-amino acid abnormalities in human disorders. Therefore, high-throughput analysis techniques are warranted to determine D-amino acids in biological fluids in a routine laboratory setting. METHODS: We developed 2 chromatographic techniques, a nonchiral derivatization with chiral (chirasil-L-val column) separation in a GC-MS system and a chiral derivatization with Marfey's reagent and LC- MS analysis. We validated the techniques for D-serine, L-serine, and glycine determination in cerebrospinal fluid (CSF), evaluated several confounders, and determined age-dependent human concentration ranges. RESULTS: Quantification limits for D-serine, L-serine, and glycine in cerebrospinal fluid were 0.14, 0.44, and 0.14 micromol/L, respectively, for GC-MS and 0.20, 0.41, and 0.14 micromol/L for LC-MS. Within-run imprecision was <3% for both methods, and between-run imprecision was <13%. Comparison of both techniques with Deming regression yielded coefficients of 0.90 (D-serine), 0.92 (L-serine), and 0.96 (glycine). Sample collection, handling, and transport is uncomplicated-there is no rostrocaudal CSF gradient, no effect of storage at 4 degrees C for 1 week before storage at -80 degrees C, and no effect of up to 3 freeze/thaw cycles. Conversely, contamination with erythrocytes increased D-serine, L-serine, and glycine concentrations. CSF concentrations for 145 apparently healthy controls demonstrated markedly and specifically increased (5 to 9 times) D-serine concentrations during early central nervous system development. CONCLUSIONS: These 2 clinically applicable analysis techniques will help to unravel pathophysiologic, diagnostic, and therapeutic issues for disorders associated with central nervous system abnormalities, NMDA-receptor dysfunction, and other pathology associated with D-amino acids.
Authors:
Sabine A Fuchs; Monique G M de Sain-van der Velden; Martina M J de Barse; Martin W Roeleveld; Margriet Hendriks; Lambertus Dorland; Leo W J Klomp; Ruud Berger; Tom J de Koning
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-07
Journal Detail:
Title:  Clinical chemistry     Volume:  54     ISSN:  1530-8561     ISO Abbreviation:  Clin. Chem.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-29     Completed Date:  2008-09-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421549     Medline TA:  Clin Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1443-50     Citation Subset:  IM    
Affiliation:
Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, Utrecht, The Netherlands. S.Fuchs@umcutrecht.nl
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Cerebrospinal Fluid / chemistry*
Child
Child, Preschool
Glycine / chemistry
Health
Humans
Infant
Infant, Newborn
Mass Spectrometry / methods*
Serine / chemistry
Stereoisomerism
Chemical
Reg. No./Substance:
56-40-6/Glycine; 56-45-1/Serine
Comments/Corrections
Comment In:
Clin Chem. 2008 Sep;54(9):1413-4   [PMID:  18755902 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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