Stable isotope dilution microquantification of creatine metabolites in plasma, whole blood and dried blood spots for pharmacological studies in mouse models of creatine deficiency.
Détails
ID Serval
serval:BIB_811627FB638E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Stable isotope dilution microquantification of creatine metabolites in plasma, whole blood and dried blood spots for pharmacological studies in mouse models of creatine deficiency.
Périodique
Clinica chimica acta; international journal of clinical chemistry
ISSN
1873-3492 (Electronic)
ISSN-L
0009-8981
Statut éditorial
Publié
Date de publication
25/09/2014
Peer-reviewed
Oui
Volume
436
Pages
160-168
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
To develop an accurate stable isotope dilution assay for simultaneous quantification of creatine metabolites ornithine, arginine, creatine, creatinine, and guanidinoacetate in very small blood sample volumes to study creatine metabolism in mice.
Liquid-chromatography (C18) tandem mass spectrometry with butylation was performed in positive ionization mode. Stable isotope dilution assay with external calibration was applied to three different specimen types, plasma, whole blood and dried blood spot (DBS).
Analytical separation, sensitivity, accuracy, and linearity of the assay were adequate. The stable isotope dilution assay in plasma revealed no significant bias to gold standard methods for the respective analytes. Compared to plasma, we observed an overestimate of creatine and creatinine (2- to 5-fold and 1.2- to 2-fold, respectively) in whole-blood and DBS, and an underestimate of arginine (2.5-fold) in DBS. Validation of the assay in mouse models of creatine deficiency revealed plasma creatine metabolite pattern in good accordance with those observed in human GAMT and AGAT deficiency. Single dose intraperitoneal application of ornithine in wild-type mice lead to fast ornithine uptake (Tmax ≤ 10 min) and elimination (T1/2=24 min), and a decline of guanidinoacetate.
The assay is fast and reliable to study creatine metabolism and pharmacokinetics in mouse models of creatine deficiency.
Liquid-chromatography (C18) tandem mass spectrometry with butylation was performed in positive ionization mode. Stable isotope dilution assay with external calibration was applied to three different specimen types, plasma, whole blood and dried blood spot (DBS).
Analytical separation, sensitivity, accuracy, and linearity of the assay were adequate. The stable isotope dilution assay in plasma revealed no significant bias to gold standard methods for the respective analytes. Compared to plasma, we observed an overestimate of creatine and creatinine (2- to 5-fold and 1.2- to 2-fold, respectively) in whole-blood and DBS, and an underestimate of arginine (2.5-fold) in DBS. Validation of the assay in mouse models of creatine deficiency revealed plasma creatine metabolite pattern in good accordance with those observed in human GAMT and AGAT deficiency. Single dose intraperitoneal application of ornithine in wild-type mice lead to fast ornithine uptake (Tmax ≤ 10 min) and elimination (T1/2=24 min), and a decline of guanidinoacetate.
The assay is fast and reliable to study creatine metabolism and pharmacokinetics in mouse models of creatine deficiency.
Mots-clé
Amidinotransferases/blood, Amidinotransferases/deficiency, Amidinotransferases/metabolism, Amino Acid Metabolism, Inborn Errors/blood, Amino Acid Metabolism, Inborn Errors/metabolism, Animals, Chromatography, Liquid, Creatine/blood, Creatine/deficiency, Creatine/metabolism, Developmental Disabilities/blood, Developmental Disabilities/metabolism, Disease Models, Animal, Dried Blood Spot Testing/methods, Guanidinoacetate N-Methyltransferase/blood, Guanidinoacetate N-Methyltransferase/deficiency, Guanidinoacetate N-Methyltransferase/metabolism, Humans, Intellectual Disability/blood, Intellectual Disability/metabolism, Isotopes/chemistry, Language Development Disorders/blood, Language Development Disorders/metabolism, Limit of Detection, Linear Models, Mice, Movement Disorders/blood, Movement Disorders/congenital, Movement Disorders/metabolism, Plasma/metabolism, Reproducibility of Results, Speech Disorders/blood, Speech Disorders/metabolism, Tandem Mass Spectrometry, Creatine deficiency syndromes, Creatine metabolites, Mouse models, Stable isotope dilution, Tandem mass spectrometry
Pubmed
Web of science
Création de la notice
15/10/2017 14:09
Dernière modification de la notice
20/08/2019 15:41
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