Show simple item record

dc.contributor.authorThorsteinsdottir, Margret
dc.contributor.authorThorsteinsdottir, Unnur A
dc.contributor.authorEiriksson, Finnur F
dc.contributor.authorRunolfsdottir, Hrafnhildur L
dc.contributor.authorAgustsdottir, Inger M Sch
dc.contributor.authorOddsdottir, Steinunn
dc.contributor.authorSigurdsson, Baldur B
dc.contributor.authorHardarson, Hordur K
dc.contributor.authorKamble, Nilesh R
dc.contributor.authorSigurdsson, Snorri Th
dc.contributor.authorEdvardsson, Vidar O
dc.contributor.authorPalsson, Runolfur
dc.date.accessioned2016-10-31T13:56:47Z
dc.date.available2016-10-31T13:56:47Z
dc.date.issued2016-11-15
dc.date.submitted2016
dc.identifier.citationQuantitative UPLC-MS/MS assay of urinary 2,8-dihydroxyadenine for diagnosis and management of adenine phosphoribosyltransferase deficiency. 2016, 1036-1037:170-177 J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.en
dc.identifier.issn1873-376X
dc.identifier.pmid27770717
dc.identifier.doi10.1016/j.jchromb.2016.09.018
dc.identifier.urihttp://hdl.handle.net/2336/620048
dc.descriptionTo access publisher's full text version of this article click on the hyperlink at the bottom of the pageen
dc.description.abstractAdenine phosphoribosyltransferase (APRT) deficiency is a hereditary disorder that leads to excessive urinary excretion of 2,8-dihydroxyadenine (DHA), causing nephrolithiasis and chronic kidney disease. Treatment with allopurinol or febuxostat reduces DHA production and attenuates the renal manifestations. Assessment of DHA crystalluria by urine microscopy is used for therapeutic monitoring, but lacks sensitivity. We report a high-throughput assay based on ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) for quantification of urinary DHA. The UPLC-MS/MS assay was optimized by a chemometric approach for absolute quantification of DHA, utilizing isotopically labeled DHA as an internal standard. Experimental screening was conducted with D-optimal design and optimization of the DHA response was performed with central composite face design and related to the peak area of DHA using partial least square regression. Acceptable precision and accuracy of the DHA concentration were obtained over a calibration range of 100 to 5000ng/mL on three different days. The intra- and inter-day accuracy and precision coefficients of variation were well within ±15% for quality control samples analyzed in replicates of six at three concentration levels. Absolute quantification of DHA in urine samples from patients with APRT deficiency was achieved wihtin 6.5min. Measurement of DHA in 24h urine samples from three patients with APRT deficiency, diluted 1:15 (v/v) with 10mM ammonium hydroxide (NH4OH), yielded a concentration of 3021, 5860 and 10563ng/mL and 24h excretion of 816, 1327 and 1649mg, respectively. A rapid and robust UPLC-MS/MS assay for absolute quantification of DHA in urine was successfully developed. We believe this method will greatly facilitate diagnosis and management of patients with APRT deficiency.
dc.description.sponsorshipRare Kidney Stone Consortium (U54DK083908), Rare Diseases Clinical Research Network (RDCRN), National Center for Advancing Translational Sciences (NCATS). National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)en
dc.languageENG
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urlhttp://dx.doi.org/ 10.1016/j.jchromb.2016.09.018en
dc.rightsArchived with thanks to Journal of chromatography. B, Analytical technologies in the biomedical and life sciencesen
dc.subjectNýrnabilunen
dc.subjectArfgengien
dc.subjectPED12
dc.subjectNEP12
dc.subject.meshAdenine Phosphoribosyltransferase/deficiencyen
dc.subject.meshSpectrophotometry, Infrareden
dc.subject.meshDrug Monitoring/therapyen
dc.subject.meshRenal Insufficiency, Chronicen
dc.subject.meshNephrolithiasisen
dc.titleQuantitative UPLC-MS/MS assay of urinary 2,8-dihydroxyadenine for diagnosis and management of adenine phosphoribosyltransferase deficiency.en
dc.typeArticleen
dc.contributor.department1University of Iceland, Reykjavik, Iceland; ArcticMass, Reykjavik, Iceland. Electronic address: margreth@hi.is. 2University of Iceland, Reykjavik, Iceland; ArcticMass, Reykjavik, Iceland. Electronic address: u.thorsteinsdottir@gmail.com. 3University of Iceland, Reykjavik, Iceland; ArcticMass, Reykjavik, Iceland. Electronic address: finnur@arcticmass.is. 4University of Iceland, Reykjavik, Iceland. Electronic address: hrafnhr@lsh.is. 5Childreńs Medical Center, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. Electronic address: ingeragu@lsh.is. 6Department of Clinical Biochemistry, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. Electronic address: steinodd@lsh.is. 7ArcticMass, Reykjavik, Iceland; Center for Biomedicine, European Academy of Bolzano/Bozen, Bolzano, Italy. Electronic address: Baldur.Sigurdsson@eurac.edu. 8University of Iceland, Reykjavik, Iceland. Electronic address: hordurkari@gmail.com. 9University of Iceland, Reykjavik, Iceland. Electronic address: nrk2@hi.is. 10University of Iceland, Reykjavik, Iceland. Electronic address: snorrisi@hi.is. 11University of Iceland, Reykjavik, Iceland; Childreńs Medical Center, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. Electronic address: vidare@lsh.is. 12University of Iceland, Reykjavik, Iceland; Division of Nephrology, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland.en
dc.identifier.journalJournal of chromatography. B, Analytical technologies in the biomedical and life sciencesen
dc.rights.accessNational Consortium - Landsaðganguren
html.description.abstractAdenine phosphoribosyltransferase (APRT) deficiency is a hereditary disorder that leads to excessive urinary excretion of 2,8-dihydroxyadenine (DHA), causing nephrolithiasis and chronic kidney disease. Treatment with allopurinol or febuxostat reduces DHA production and attenuates the renal manifestations. Assessment of DHA crystalluria by urine microscopy is used for therapeutic monitoring, but lacks sensitivity. We report a high-throughput assay based on ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) for quantification of urinary DHA. The UPLC-MS/MS assay was optimized by a chemometric approach for absolute quantification of DHA, utilizing isotopically labeled DHA as an internal standard. Experimental screening was conducted with D-optimal design and optimization of the DHA response was performed with central composite face design and related to the peak area of DHA using partial least square regression. Acceptable precision and accuracy of the DHA concentration were obtained over a calibration range of 100 to 5000ng/mL on three different days. The intra- and inter-day accuracy and precision coefficients of variation were well within ±15% for quality control samples analyzed in replicates of six at three concentration levels. Absolute quantification of DHA in urine samples from patients with APRT deficiency was achieved wihtin 6.5min. Measurement of DHA in 24h urine samples from three patients with APRT deficiency, diluted 1:15 (v/v) with 10mM ammonium hydroxide (NH4OH), yielded a concentration of 3021, 5860 and 10563ng/mL and 24h excretion of 816, 1327 and 1649mg, respectively. A rapid and robust UPLC-MS/MS assay for absolute quantification of DHA in urine was successfully developed. We believe this method will greatly facilitate diagnosis and management of patients with APRT deficiency.


Files in this item

Thumbnail
Name:
Publisher version

This item appears in the following Collection(s)

Show simple item record