Mass Spectrometric Applications for Diagnosing Metabolic and Endocrine Diseases

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003		SwePub
008		080422s2008 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
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041		a engb eng
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100	1	a Kushnir, Mark M.,d 1957-u Uppsala universitet,Analytisk kemi4 aut
245	1 0	a Mass Spectrometric Applications for Diagnosing Metabolic and Endocrine Diseases
264	1	a Uppsala :b Acta Universitatis Upsaliensis,c 2008
300		a 80 s.
338		a electronic2 rdacarrier
490	0	a Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology,x 1651-6214 ;v 426
520		a Disease-specific compounds (biomarkers) are analyzed in clinical laboratories to assist with diagnosing diseases. This thesis describes development and validation of liquid chromatography tandem mass spectrometry (LC-MS/MS) based tests for diagnosing a diverse group of endocrine and metabolic diseases. The analytical methods used on-line and off-line sample extraction and analytical derivatization as means of enhancing the analytical sensitivity, specificity and clinical utility. All developed methods were extensively validated and reference intervals for the biomarker concentrations were established in blood samples of healthy adults and children. Advantages of the LC-MS/MS as an analytical technique include possibility of simultaneous measurement of multiple analytes and ability of confirming their identity. In this thesis we proposed and evaluated approaches for the assessment of the specificity of analysis in the methods that use tandem mass spectrometry detection. To enhance throughput of the LC-MS/MS tests for the biomarkers that have endogenous or exogenous isomers an approach was developed for quantitation of isomers from unresolved chromatographic peaks. Using methods developed in this thesis we performed a study of the steroidogenesis in ovarian follicles of healthy women and women with polycystic ovary syndrome (PCOS). Obtained data on the steroid concentrations and associations between the steroid metabolites in the pathway would be helpful for better understanding of the ovarian pathophysiology. Potential biomarkers of PCOS were identified in the thesis; further studies will be necessary to confirm their clinical utility.
653		a Analytical chemistry
653		a biomarker
653		a liquid chromatography
653		a tandem mass spectrometry
653		a LC-MS/MS
653		a sample preparation
653		a isomers
653		a steroid hormones
653		a congenital adrenal hyperplasia
653		a polycystic ovary syndrome
653		a Analytisk kemi
700	1	a Bergquist, Jonas4 ths
700	1	a Rockwood, Alan L4 ths
700	1	a Herold, David,c Professoru Department of Pathology, University of California, San Diego4 opn
710	2	a Uppsala universitetb Analytisk kemi4 org
856	4	u https://uu.diva-portal.org/smash/get/diva2:171886/FULLTEXT01.pdfx primaryx Raw objecty fulltext
856	4	u https://uu.diva-portal.org/smash/get/diva2:171886/COVER01.pdfy cover
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8658

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Av författaren/redakt...: Kushnir, Mark M. ...; Bergquist, Jonas; Rockwood, Alan L; Herold, David, P ...

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Av lärosätet: Uppsala universitet

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