Universität zu Köln

Goergens, Christian, Guddat, Sven, Schaenzer, Wilhelm and Thevis, Mario (2014). Screening and confirmation of myo-inositol trispyrophosphate (ITPP) in human urine by hydrophilic interaction liquid chromatography high resolution / high accuracy mass spectrometry for doping control purposes. Drug Test. Anal., 6 (11-12). S. 1102 - 1108. HOBOKEN: WILEY. ISSN 1942-7611

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Abstract

Myo-inositol trispyrophosphate (ITPP) is a novel allosteric effector of haemoglobin with high permeation selectivity across the red blood cell plasma membrane. Due to its potential to reduce the oxygen affinity of haemoglobin, ITPP application results in an enhanced oxygen release in hypoxic tissues. Therefore, ITPP is being examined for the treatment of numerous illnesses that involve hypoxia, such as cardiovascular diseases, cancer or Alzheimer's disease. Similar to the prohibited substance Efaproxiral (R), ITPP increases maximal exercise capacity in mice, providing high potential to be misused in sports. To keep up with cheating athletes, a fast and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for screening and confirmation of ITPP in human urine for doping control purposes was developed. According to the molecule's distinct hydrophilic properties, extraction from complex biological matrices is challenging and conventional reversed phase liquid chromatography (RPLC) separations are not suitable for its detection. Therefore an approach based on hydrophilic interaction liquid chromatography (HILIC) Orbitrap mass spectrometry was established. The methodology was fully validated for qualitative purposes. Screening and confirmation assay are characterized by satisfactory specificity and robustness, adequate intra-day (screening: 4.9-8.1%; confirmation: 2.0-6.7%) and inter-day precision (screening: 4.6-9.1%; confirmation: 1.8-6.6%), excellent linear correlations (>0.99) with sufficient LLOD in the sub ng/mL range (screening: 15ng/mL; confirmation: 1ng/mL). In addition it could be shown that ITPP is stable in human urine under the mandatory storage period and conditions for doping control laboratories. To our knowledge, this is the first validated dilute-and-inject' LC-MS/MS method for the reliable detection of ITPP in human urine. Copyright (c) 2014 John Wiley & Sons, Ltd.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Goergens, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Guddat, Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaenzer, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-423920
DOI:	10.1002/dta.1700
Journal or Publication Title:	Drug Test. Anal.
Volume:	6
Number:	11-12
Page Range:	S. 1102 - 1108
Date:	2014
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1942-7611
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ALLOSTERIC EFFECTOR; ORGANIC-PHOSPHATES; EFAPROXIRAL RSR13; EXERCISE CAPACITY; HEMOGLOBIN; PERFORMANCE; SELECTIVITY; MECHANISMS; SEPARATION; PLASMA Multiple languages Biochemical Research Methods; Chemistry, Analytical; Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42392