BMC Seminar Thursday 28th of March at 12:00 in room 201 Læknagarður

Speaker: Unnur Þorsteinsdóttir, PhD student under supervision of Prof. Margrét Þorsteinsdóttir, Faulty of Pharmaceutical Sciences, University of Iceland

Title: Mass Spectrometry based assay for diagnosis of APRT deficiency

Abstract: Adenine phosphoribosyltransferase (APRT) deficiency is a rare kidney stone disease that results in excessive urinary excretion of poorly soluble 2,8-dihydroxyadenine (DHA), causing nephrolithiasis and chronic kidney disease (CKD). Treatment with allopurinol and febuxostat effectively reduces DHA excretion and prevents urinary stone formation. A reliable method for diagnosis and therapeutic drug monitoring of patients with APRT deficiency is needed.

The aim of this project was to develop and optimize a ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay for quantification of DHA and the pharmaceutical agents allopurinol and febuxostat in urine and plasma for diagnosis and therapeutic monitoring of patients with APRT deficiency. The UPLC-MS/MS assay developed can also determine other purines involved in the adenine metabolic pathway in the same analytical run.

The UPLC-MS/MS plasma and urine assays will significantly enhance the diagnosis of APRT deficiency and monitoring of pharmacotherapy. Earlier diagnosis of the disorder will facilitate the institution of timely pharmacotherapy and prevention of kidney stone episodes and progressive CKD and would thus be likely to improve the outcomes of patients with this disorder.