Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Sigmund, Gerd UNSPECIFIED UNSPECIFIED UNSPECIFIED Thomas, Andreas UNSPECIFIED orcid.org/0000-0003-1199-0743 UNSPECIFIED Vogel, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Walpurgis, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED Kwiatkowska, Dorota UNSPECIFIED UNSPECIFIED UNSPECIFIED Geyer, Hans UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaenzer, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language HEALTHY ADULT VOLUNTEERS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; D-AMPHETAMINE; OPEN-LABEL; DIMESYLATE; PHARMACOKINETICS; CROSSOVER; CHILDREN Multiple languages Biochemical Research Methods; Chemistry, Analytical; Spectroscopy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44066