PMID- 24573809
OWN - NLM
STAT- MEDLINE
DCOM- 20141022
LR  - 20151119
IS  - 1097-0231 (Electronic)
IS  - 0951-4198 (Linking)
VI  - 28
IP  - 7
DP  - 2014 Apr 15
TI  - Isotope-dilution mass spectrometric quantification of the prodrug 
      lisdexamfetamine in human urine in doping control analysis.
PG  - 781-6
LID - 10.1002/rcm.6844 [doi]
AB  - 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.
CI  - Copyright (c) 2014 John Wiley & Sons, Ltd.
FAU - Thevis, Mario
AU  - Thevis M
AD  - Institute of Biochemistry - Center for Preventive Doping Research, German Sport 
      University Cologne, Am Sportpark Mungersdorf 6, 50933, Cologne, Germany.
FAU - Sigmund, Gerd
AU  - Sigmund G
FAU - Thomas, Andreas
AU  - Thomas A
FAU - Vogel, Matthias
AU  - Vogel M
FAU - Walpurgis, Katja
AU  - Walpurgis K
FAU - Kwiatkowska, Dorota
AU  - Kwiatkowska D
FAU - Geyer, Hans
AU  - Geyer H
FAU - Schanzer, Wilhelm
AU  - Schanzer W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Rapid Commun Mass Spectrom
JT  - Rapid communications in mass spectrometry : RCM
JID - 8802365
RN  - 0 (Prodrugs)
RN  - SJT761GEGS (Lisdexamfetamine Dimesylate)
RN  - TZ47U051FI (Dextroamphetamine)
SB  - IM
MH  - Dextroamphetamine/chemistry/*urine
MH  - *Doping in Sports
MH  - Female
MH  - Humans
MH  - Limit of Detection
MH  - Linear Models
MH  - Lisdexamfetamine Dimesylate
MH  - Male
MH  - Mass Spectrometry/*methods
MH  - Prodrugs
MH  - Reproducibility of Results
EDAT- 2014/02/28 06:00
MHDA- 2014/10/23 06:00
CRDT- 2014/02/28 06:00
PHST- 2013/11/27 00:00 [received]
PHST- 2014/01/15 00:00 [accepted]
PHST- 2014/02/28 06:00 [entrez]
PHST- 2014/02/28 06:00 [pubmed]
PHST- 2014/10/23 06:00 [medline]
AID - 10.1002/rcm.6844 [doi]
PST - ppublish
SO  - Rapid Commun Mass Spectrom. 2014 Apr 15;28(7):781-6. doi: 10.1002/rcm.6844.