A sensitive and simple ultra-high-performance-liquid chromatography-tandem mass spectrometry based method for the quantification of d-amino acids in body fluids
(2011) In Journal of Chromatography A 1218(40). p.7130-7136- Abstract
d-Amino acids are increasingly being recognized as important signaling molecules in mammals, including humans. d-Serine and d-aspartate are believed to act as signaling molecules in the central nervous system. Interestingly, several other d-amino acids also occur in human plasma, but very little is currently known regarding their function and origin. Abnormal levels of d-amino acids have been implicated in the pathogenesis of different diseases, including schizophrenia and amyotrophic lateral sclerosis (ALS), indicating that d-amino acid levels hold potential as diagnostic markers. Research into the biological functions of d-amino acids is hindered, however, by the lack of sufficiently sensitive, high-throughput analytical methods. In... (More)
d-Amino acids are increasingly being recognized as important signaling molecules in mammals, including humans. d-Serine and d-aspartate are believed to act as signaling molecules in the central nervous system. Interestingly, several other d-amino acids also occur in human plasma, but very little is currently known regarding their function and origin. Abnormal levels of d-amino acids have been implicated in the pathogenesis of different diseases, including schizophrenia and amyotrophic lateral sclerosis (ALS), indicating that d-amino acid levels hold potential as diagnostic markers. Research into the biological functions of d-amino acids is hindered, however, by the lack of sufficiently sensitive, high-throughput analytical methods. In particular, the interference of large amounts of l-amino acids in biological samples and the low concentrations of d-amino acids are challenging. In this paper, we compared 7 different chiral derivatization agents for the analysis of d-amino acids and show that the chiral reagent (S)-NIFE offers outstanding performance in terms of sensitivity and enantioselectivity. An UPLC-MS/MS based method for the quantification of d-amino acids human biological fluids was then developed using (S)-NIFE. Baseline separation (R s>2.45) was achieved for the isomers of all 19 chiral proteinogenic amino acids. The limit of detection was <1nM for all amino acids except d-alanine (1.98nM), d-methionine (1.18nM) and d-asparagine (5.15nM). For measurements in human plasma, cerebrospinal fluid and urine, the accuracy ranged between 85% and 107%. The intra-assay and inter-assay were both <16% RSD for these three different matrices. Importantly, the method does not suffer from spontaneous racemization during sample preparation and derivatization. Using the described method, d-amino acid levels in human cerebrospinal fluid, plasma and urine were measured.
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- author
- Visser, Wouter F. ; Verhoeven-Duif, Nanda M. ; Ophoff, Roel ; Bakker, Steven ; Klomp, Leo W. ; Berger, Ruud and De Koning, Tom J. LU
- publishing date
- 2011-10-07
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- (S)-NIFE, Chiral derivatization, D-Amino acids, Diagnostic markers
- in
- Journal of Chromatography A
- volume
- 1218
- issue
- 40
- pages
- 7 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:21890145
- scopus:80052617957
- ISSN
- 0021-9673
- DOI
- 10.1016/j.chroma.2011.07.087
- language
- English
- LU publication?
- no
- id
- dbc583a0-4d2a-4b64-8f18-2473071336b4
- date added to LUP
- 2020-02-26 10:18:32
- date last changed
- 2024-04-17 05:35:01
@article{dbc583a0-4d2a-4b64-8f18-2473071336b4,
abstract = {{<p>d-Amino acids are increasingly being recognized as important signaling molecules in mammals, including humans. d-Serine and d-aspartate are believed to act as signaling molecules in the central nervous system. Interestingly, several other d-amino acids also occur in human plasma, but very little is currently known regarding their function and origin. Abnormal levels of d-amino acids have been implicated in the pathogenesis of different diseases, including schizophrenia and amyotrophic lateral sclerosis (ALS), indicating that d-amino acid levels hold potential as diagnostic markers. Research into the biological functions of d-amino acids is hindered, however, by the lack of sufficiently sensitive, high-throughput analytical methods. In particular, the interference of large amounts of l-amino acids in biological samples and the low concentrations of d-amino acids are challenging. In this paper, we compared 7 different chiral derivatization agents for the analysis of d-amino acids and show that the chiral reagent (S)-NIFE offers outstanding performance in terms of sensitivity and enantioselectivity. An UPLC-MS/MS based method for the quantification of d-amino acids human biological fluids was then developed using (S)-NIFE. Baseline separation (R <sub>s</sub>>2.45) was achieved for the isomers of all 19 chiral proteinogenic amino acids. The limit of detection was <1nM for all amino acids except d-alanine (1.98nM), d-methionine (1.18nM) and d-asparagine (5.15nM). For measurements in human plasma, cerebrospinal fluid and urine, the accuracy ranged between 85% and 107%. The intra-assay and inter-assay were both <16% RSD for these three different matrices. Importantly, the method does not suffer from spontaneous racemization during sample preparation and derivatization. Using the described method, d-amino acid levels in human cerebrospinal fluid, plasma and urine were measured.</p>}},
author = {{Visser, Wouter F. and Verhoeven-Duif, Nanda M. and Ophoff, Roel and Bakker, Steven and Klomp, Leo W. and Berger, Ruud and De Koning, Tom J.}},
issn = {{0021-9673}},
keywords = {{(S)-NIFE; Chiral derivatization; D-Amino acids; Diagnostic markers}},
language = {{eng}},
month = {{10}},
number = {{40}},
pages = {{7130--7136}},
publisher = {{Elsevier}},
series = {{Journal of Chromatography A}},
title = {{A sensitive and simple ultra-high-performance-liquid chromatography-tandem mass spectrometry based method for the quantification of d-amino acids in body fluids}},
url = {{http://dx.doi.org/10.1016/j.chroma.2011.07.087}},
doi = {{10.1016/j.chroma.2011.07.087}},
volume = {{1218}},
year = {{2011}},
}