Isotope‐dilution mass spectrometric quantification of the prodrug lisdexamfetamine in human urine in doping control analysis. (14th February 2014)

• Record Type: Journal Article
• Authors: Thevis, Mario; Sigmund, Gerd; Thomas, Andreas; Vogel, Matthias; Walpurgis, Katja; Kwiatkowska, Dorota; Geyer, Hans; Schänzer, Wilhelm
• Is Part Of: Rapid communications in mass spectrometry. Volume 28:Number 7(2014)
• Page Start: 781
• Page End: 786
• Publication Date: 2014-02-14
• Subjects: Mass spectrometry -- Periodicals; 543.65
• DOI: 10.1002/rcm.6844
• Languages: English
• ISSNs: 0951-4198

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="rcm6844-sec-0001" sec-type="section"> <title>RATIONALE</title> <p>Therapeutic approaches concerning attention‐deficit hyperactivity disorder (ADHD) commonly include the administration of drugs amplifying cerebral dopamine and norepinephrine signals. Among these, compounds belonging to the Prohibited List as established by the World Anti‐Doping Agency (WADA) are present such as amfetamine or methylphenidate, and abuse of these can result in sanctions for athletes. The recently approved therapeutic lisdexamfetamine represents a slow‐release prodrug of amfetamine for ADHD treatment. In order to support doping control laboratories in differentiating the abuse of amfetamine from a therapeutic administration of lisdexamfetamine, the determination of the prodrug from urine is desirable. Since approximately 2% of lisdexamfetamine are eliminated intact into urine, a liquid chromatography/high‐resolution/high accuracy mass spectrometric method was developed, allowing the target analyte and one of its metabolites (4‐hydroxyamfetamine sulfate) to be accurately quantified.</p> </sec> <sec id="rcm6844-sec-0002" sec-type="section"> <title>METHODS</title> <p>Urine samples were fortified with fourfold deuterated lisdexamfetamine and analyzed directly using ultrahigh‐performance liquid chromatography (UHPLC) interfaced via electrospray ionization to a second‐generation quadrupole‐orbitrap mass spectrometer. The assay was characterized concerning specificity, limits of quantification (0.15–5 ng/mL), intraday and interday imprecision (4–22%), accuracy (90–120%), linearity, and ion suppression/enhancement effects. A patient's urine samples were analyzed to provide proof‐of‐principle data demonstrating that the intact prodrug lisdexamfetamine is detectable in urine up to 11 h post‐administration at concentrations up to 80 ng/mL. Moreover, amfetamine and sulfoconjugated 4‐hydroxyamfetamine were measured, yielding up to 1146 and 56 ng/mL, respectively.</p> </sec> <sec id="rcm6844-sec-0003" sec-type="section"> <title>CONCLUSIONS</title> <p>Considering the observed comparably low urinary concentrations of lisdexamfetamine and 4‐hydroxyamfetamine sulfate, the preferred minimally labor‐intense sample preparation, and the necessity of fast and robust result generation, the employed instrumental setup proved fit‐for‐purpose in sports drug testing. Copyright © 2014 John Wiley & Sons, Ltd.</p> </sec> </abstract>