Thevis, Mario, Sigmund, Gerd, Thomas, Andreas ORCID: 0000-0003-1199-0743, Vogel, Matthias, Walpurgis, Katja, Kwiatkowska, Dorota, Geyer, Hans and Schaenzer, Wilhelm (2014). Isotope-dilution mass spectrometric quantification of the prodrug lisdexamfetamine in human urine in doping control analysis. Rapid Commun. Mass Spectrom., 28 (7). S. 781 - 787. HOBOKEN: WILEY-BLACKWELL. ISSN 1097-0231

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Abstract

RATIONALE 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. METHODS 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. CONCLUSIONS 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 (c) 2014 John Wiley & Sons, Ltd.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Thevis, MarioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sigmund, GerdUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomas, AndreasUNSPECIFIEDorcid.org/0000-0003-1199-0743UNSPECIFIED
Vogel, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walpurgis, KatjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kwiatkowska, DorotaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Geyer, HansUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaenzer, WilhelmUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-440667
DOI: 10.1002/rcm.6844
Journal or Publication Title: Rapid Commun. Mass Spectrom.
Volume: 28
Number: 7
Page Range: S. 781 - 787
Date: 2014
Publisher: WILEY-BLACKWELL
Place of Publication: HOBOKEN
ISSN: 1097-0231
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
HEALTHY ADULT VOLUNTEERS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; D-AMPHETAMINE; OPEN-LABEL; DIMESYLATE; PHARMACOKINETICS; CROSSOVER; CHILDRENMultiple languages
Biochemical Research Methods; Chemistry, Analytical; SpectroscopyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/44066

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