Improved diagnostics of purine and pyrimidine metabolism disorders using LC-MS/MS and its clinical application
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F23%3A10465237" target="_blank" >RIV/00064165:_____/23:10465237 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/23:10465237
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=KD4dGPPG2q" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=KD4dGPPG2q</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1515/cclm-2022-1236" target="_blank" >10.1515/cclm-2022-1236</a>
Alternative languages
Result language
angličtina
Original language name
Improved diagnostics of purine and pyrimidine metabolism disorders using LC-MS/MS and its clinical application
Original language description
Objectives: To develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify 41 different purine and pyrimidine (PuPy) metabolites in human urine to allow detection of most known disorders in this metabolic pathway and to determine reference intervals. Methods: Urine samples were diluted with an aqueous buffer to minimize ion suppression. For detection and quantification, liquid chromatography was combined with electrospray ionization, tandem mass spectrometry and multiple reaction monitoring. Transitions and instrument settings were established to quantify 41 analytes and nine stable-isotope-labeled internal standards (IS). Results: The established method is precise (intra-day CV: 1.4-6.3%; inter-day CV: 1.3-15.2%), accurate (95.2% external quality control results within +/- 2 SD and 99.0% within +/- 3 SD; analyte recoveries: 61-121%), sensitive and has a broad dynamic range to quantify normal and pathological metabolite concentrations within one run. All analytes except aminoimidazole ribonucleoside (AIr) are stable before, during and after sample preparation. Moreover, analytes are not affected by five cycles of freeze-thawing (variation: -5.6 to 7.4%), are stable in thymol (variation: -8.4 to 12.9%) and the lithogenic metabolites also in HCl conserved urine. Age-dependent reference intervals from 3,368 urine samples were determined and used to diagnose 11 new patients within 7 years (total performed tests: 4,206). Conclusions: The presented method and reference intervals enable the quantification of 41 metabolites and the potential diagnosis of up to 25 disorders of PuPy metabolism.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30100 - Basic medicine
Result continuities
Project
<a href="/en/project/LX22NPO5107" target="_blank" >LX22NPO5107: National institute for Neurological Research</a><br>
Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Clinical Chemistry and Laboratory Medicine
ISSN
1434-6621
e-ISSN
1437-4331
Volume of the periodical
61
Issue of the periodical within the volume
10
Country of publishing house
DE - GERMANY
Number of pages
10
Pages from-to
1792-1801
UT code for WoS article
000964178900001
EID of the result in the Scopus database
2-s2.0-85151897151