Höfundar:
Margret Thorsteinsdottir, Unnur Arna Thorsteinsdottir, Kristrun Yr Holm, Kari Arnarson, Sigridur Klara Boðvarsdottir, Finnur Freyr Eiriksson
Introduction: Majority of targeted clinical analysis are still performed with immunoassays even though these techniques are susceptible to interference and are difficult to multiplex. These problems can be overcome by mass spectrometry (MS)-based assays. Ultra-performance liquid chromatography (UPLC) coupled to quadrupole time-of-flight mass spectrometer is an excellent platform for untargeted analysis while UPLC coupled to triple quadrupole mass spectrometer (UPLC-MS/MS) gives ultimate selectivity and sensitivity needed for quantification of biomarkers in biological matrices. MS-based assays for early dignosis of breast cancer and for diagnosis and therapeutic monitoring in patients with adenine phosphoribosyltransferase deficiency (APRTd) will be presented.
Methods: A UPLC-MS/MS platform was used for targeted proteomic analysis of bio-bank plasma samples from breast cancer (BC) patients and healthy controls. In another study, design of experiments (DoE) was used for optimization of UPLC-MS/MS assay for absolute quantification of 2,8-dihydroxyadenine, adenine, allopurinol, oxypurinol and febuxostat in urine and plasma samples from untreated and treated patients with APRTd and healthy controls.
Results: The targeted proteomic MS-assay revealed a potential difference in protein composition in plasma samples from BC patients and healthy controls. In the other case study, a reliable clinical UPLC-MS/MS assay for simultaneous quantification of biomarkers in urine and plasma was successfully optimized by DoE for diagnosis and therapeutic monitoring of patients with APRTd.
Conclusions: The clinical mass spectrometry assays provide opportunity for non-invasive diagnostic tools (on e.g. plasma samples), improved accurate early diagnosis of the diseases and gives the opportunity towards a personalized treatment with potentially improved outcomes of the patients.