Two mass-spectrometric techniques for quantifying serine enantiomers and glycine in cerebrospinal fluid : Potential confounders and age-dependent ranges
(2008) In Clinical Chemistry 54(9). p.1443-1450- Abstract
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... (More)
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 μmol/L, respectively, for GC-MS and 0.20, 0.41, and 0.14 μmol/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 (Dserine), 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 °C for 1 week before storage at -80 °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.
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- author
- Fuchs, Sabine A. ; De Sain-van Der Velden, Monique G.M. ; De Barse, Martina M.J. ; Roeleveld, Martin W. ; Hendriks, Margriet ; Dorland, Lambertus ; Klomp, Leo W.J. ; Berger, Ruud and De Koning, Tom J. LU
- publishing date
- 2008-08-09
- type
- Contribution to journal
- publication status
- published
- in
- Clinical Chemistry
- volume
- 54
- issue
- 9
- pages
- 1443 - 1450
- publisher
- American Association for Clinical Chemistry
- external identifiers
-
- pmid:18606633
- scopus:51349162646
- ISSN
- 0009-9147
- DOI
- 10.1373/clinchem.2007.100412
- language
- English
- LU publication?
- no
- id
- 77f2d5f5-fb9f-42fd-b2f4-8a3a7313b62e
- date added to LUP
- 2020-02-28 13:52:46
- date last changed
- 2024-04-03 02:13:37
@article{77f2d5f5-fb9f-42fd-b2f4-8a3a7313b62e,
abstract = {{<p>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 μmol/L, respectively, for GC-MS and 0.20, 0.41, and 0.14 μmol/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 (Dserine), 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 °C for 1 week before storage at -80 °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.</p>}},
author = {{Fuchs, Sabine A. and De Sain-van Der Velden, Monique G.M. and De Barse, Martina M.J. and Roeleveld, Martin W. and Hendriks, Margriet and Dorland, Lambertus and Klomp, Leo W.J. and Berger, Ruud and De Koning, Tom J.}},
issn = {{0009-9147}},
language = {{eng}},
month = {{08}},
number = {{9}},
pages = {{1443--1450}},
publisher = {{American Association for Clinical Chemistry}},
series = {{Clinical Chemistry}},
title = {{Two mass-spectrometric techniques for quantifying serine enantiomers and glycine in cerebrospinal fluid : Potential confounders and age-dependent ranges}},
url = {{http://dx.doi.org/10.1373/clinchem.2007.100412}},
doi = {{10.1373/clinchem.2007.100412}},
volume = {{54}},
year = {{2008}},
}