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Investigation of urinary excretion of hydroxyethyl starch and dextran by uhplc-hrms in different acquisition modes.

Esposito S, Deventer K, Giron AJ, Roels K, Herregods L, Verstraete A, Van Eenoo P - Biol Sport (2014)

Bottom Line: In-source fragmentation yielded the best results in terms of limit of detection (LOD) and detection times, whereas detection of HES and dextran metabolites in full scan mode with no in-source fragmentation is related to recent administration (< 24 hours).Urinary excretion studies showed detection windows for HES and dextran respectively of 72 and 48 hours after administration.Dextran concentrations were above the previously proposed threshold of 500 µg · mL(-1) for 12 hours.

View Article: PubMed Central - PubMed

Affiliation: Doping Control Laboratory, Ghent University (UGent), Technologiepark 30, 9052 Zwijnaarde, Belgium.

ABSTRACT
Plasma volume expanders (PVEs) such as hydroxyethyl starch (HES) and dextran are misused in sports because they can prevent dehydration and reduce haematocrit values to mask erythropoietin abuse. Endogenous hydrolysis generates multiple HES and dextran oligosaccharides which are excreted in urine. Composition of the urinary metabolic profiles of PVEs varies depending on post-administration time and can have an impact on their detectability. In this work, different mass spectrometry data acquisition modes (full scan with and without in-source collision-induced dissociation) were used to study urinary excretion profiles of HES and dextran, particularly by investigating time-dependent detectability of HES and dextran urinary oligosaccharide metabolites in post-administration samples. In-source fragmentation yielded the best results in terms of limit of detection (LOD) and detection times, whereas detection of HES and dextran metabolites in full scan mode with no in-source fragmentation is related to recent administration (< 24 hours). Urinary excretion studies showed detection windows for HES and dextran respectively of 72 and 48 hours after administration. Dextran concentrations were above the previously proposed threshold of 500 µg · mL(-1) for 12 hours. A "dilute-and-shoot" method for the detection of HES and dextran in human urine by ultra-high-pressure liquid chromatography-electrospray ionization-high resolution Orbitrap™ mass spectrometry was developed for this study. Validation of the method showed an LOD in the range of 10-500 µg · mL(-1) for the most significant HES and dextran metabolites in the different modes. The method allows retrospective data analysis and can be implemented in existing high-resolution mass spectrometry-based doping control screening analysis.

No MeSH data available.


Related in: MedlinePlus

COMPARISON BETWEEN MS RESPONSE OF DIFFERENT ION TYPES FOR THE REPRESENTATIVE HES METABOLITE Glu2HE1 (LEFT) AND DEXTRAN METABOLITE GLU3 (RIGHT) IN REFERENCE STANDARD SOLUTIONS
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Figure 0002: COMPARISON BETWEEN MS RESPONSE OF DIFFERENT ION TYPES FOR THE REPRESENTATIVE HES METABOLITE Glu2HE1 (LEFT) AND DEXTRAN METABOLITE GLU3 (RIGHT) IN REFERENCE STANDARD SOLUTIONS

Mentions: HES and dextran showed very similar ionization properties. In fact, when detecting HES and dextran, multiple ions were recorded both in positive ([M+H]+, [M+Na]+, [M-K]+, [M-H2O+Na]+, [M+NH4]+) and in negative mode ([M-H]-, [M+FA]- and [M-H2O-H]-). Relative abundances of the ion types of interest varied significantly. Overall, positive mode yielded the best results. In particular, [M+H]+, [M+Na]+, [M+K]+ and [M-H2O+H]+ gave the best MS response and allowed for the longest detection window. For both PVEs, abundances of Na+ and K+ adducts were generally comparable for the two different acquisition modes, whereas peaks of protonated ions were generally higher when isCID was used (Figure 2). Also negative ionization was observed, as previously described by Cmelik et al. [3], but showed less sensitivity than the positive mode.


Investigation of urinary excretion of hydroxyethyl starch and dextran by uhplc-hrms in different acquisition modes.

Esposito S, Deventer K, Giron AJ, Roels K, Herregods L, Verstraete A, Van Eenoo P - Biol Sport (2014)

COMPARISON BETWEEN MS RESPONSE OF DIFFERENT ION TYPES FOR THE REPRESENTATIVE HES METABOLITE Glu2HE1 (LEFT) AND DEXTRAN METABOLITE GLU3 (RIGHT) IN REFERENCE STANDARD SOLUTIONS
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4042655&req=5

Figure 0002: COMPARISON BETWEEN MS RESPONSE OF DIFFERENT ION TYPES FOR THE REPRESENTATIVE HES METABOLITE Glu2HE1 (LEFT) AND DEXTRAN METABOLITE GLU3 (RIGHT) IN REFERENCE STANDARD SOLUTIONS
Mentions: HES and dextran showed very similar ionization properties. In fact, when detecting HES and dextran, multiple ions were recorded both in positive ([M+H]+, [M+Na]+, [M-K]+, [M-H2O+Na]+, [M+NH4]+) and in negative mode ([M-H]-, [M+FA]- and [M-H2O-H]-). Relative abundances of the ion types of interest varied significantly. Overall, positive mode yielded the best results. In particular, [M+H]+, [M+Na]+, [M+K]+ and [M-H2O+H]+ gave the best MS response and allowed for the longest detection window. For both PVEs, abundances of Na+ and K+ adducts were generally comparable for the two different acquisition modes, whereas peaks of protonated ions were generally higher when isCID was used (Figure 2). Also negative ionization was observed, as previously described by Cmelik et al. [3], but showed less sensitivity than the positive mode.

Bottom Line: In-source fragmentation yielded the best results in terms of limit of detection (LOD) and detection times, whereas detection of HES and dextran metabolites in full scan mode with no in-source fragmentation is related to recent administration (< 24 hours).Urinary excretion studies showed detection windows for HES and dextran respectively of 72 and 48 hours after administration.Dextran concentrations were above the previously proposed threshold of 500 µg · mL(-1) for 12 hours.

View Article: PubMed Central - PubMed

Affiliation: Doping Control Laboratory, Ghent University (UGent), Technologiepark 30, 9052 Zwijnaarde, Belgium.

ABSTRACT
Plasma volume expanders (PVEs) such as hydroxyethyl starch (HES) and dextran are misused in sports because they can prevent dehydration and reduce haematocrit values to mask erythropoietin abuse. Endogenous hydrolysis generates multiple HES and dextran oligosaccharides which are excreted in urine. Composition of the urinary metabolic profiles of PVEs varies depending on post-administration time and can have an impact on their detectability. In this work, different mass spectrometry data acquisition modes (full scan with and without in-source collision-induced dissociation) were used to study urinary excretion profiles of HES and dextran, particularly by investigating time-dependent detectability of HES and dextran urinary oligosaccharide metabolites in post-administration samples. In-source fragmentation yielded the best results in terms of limit of detection (LOD) and detection times, whereas detection of HES and dextran metabolites in full scan mode with no in-source fragmentation is related to recent administration (< 24 hours). Urinary excretion studies showed detection windows for HES and dextran respectively of 72 and 48 hours after administration. Dextran concentrations were above the previously proposed threshold of 500 µg · mL(-1) for 12 hours. A "dilute-and-shoot" method for the detection of HES and dextran in human urine by ultra-high-pressure liquid chromatography-electrospray ionization-high resolution Orbitrap™ mass spectrometry was developed for this study. Validation of the method showed an LOD in the range of 10-500 µg · mL(-1) for the most significant HES and dextran metabolites in the different modes. The method allows retrospective data analysis and can be implemented in existing high-resolution mass spectrometry-based doping control screening analysis.

No MeSH data available.


Related in: MedlinePlus