Identification of oral antidiabetics and their metabolites in human urine by liquid chromatography/tandem mass spectrometry - a matter for doping control analysis

摘要

Since 1999, insulin belongs to the list of prohibited substances of the International Olympic Committee and the World Anti-Doping Agency. Except for patients suffering from insulin-dependent diabetes mellitus, the administration of insulin is not allowed. Therapeutics developed to treat noninsulin-dependent diabetes mellitus act as releasing factors of endogenously produced insulin or improve its efficiency mediating the glucose uptake into insulin-dependent tissues. Hence, these compounds are also relevant for sports drug testing, and a fast, robust, and sensitive assay was developed to identify 12 oral antidiabetic agents or respective hydroxylated metabolites in human urine. Urine specimens are enzymatically hydrolyzed; target analytes are extracted by liquid-liquid extraction and identified by means of liquid chromatography interfaced to tandem mass spectrometry by electrospray ionization. Detection limits of respective drugs ranged between 10 and 30 ng/mL, metabolites of therapeutics were characterized by diagnostic fragmentation pathways upon collisionally activated dissociation of protonated molecules, and general fragmentation routes were proposed. Copyright (c) 2005 John Wiley S Sons, Ltd.