Limits...
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

SEMI-QUANTITATIVE DETERMINATION OF [Glu3-H2O+H]+ CONCENTRATION IN A REPRESENTATIVE BATCH OF ROUTINE SAMPLES (N= 50), COMPARED TO A QUALITY CONTROL SAMPLE SPIKED AT 500 µg · mL−1 IN FSMS (A) AND ISCID (B) MODE AND 3, 12 AND 24 HOURS EXCRETION SAMPLES.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4042655&req=5

Figure 0006: SEMI-QUANTITATIVE DETERMINATION OF [Glu3-H2O+H]+ CONCENTRATION IN A REPRESENTATIVE BATCH OF ROUTINE SAMPLES (N= 50), COMPARED TO A QUALITY CONTROL SAMPLE SPIKED AT 500 µg · mL−1 IN FSMS (A) AND ISCID (B) MODE AND 3, 12 AND 24 HOURS EXCRETION SAMPLES.

Mentions: Compared to HES, selectivity is a bigger issue for dextran because physiopathological excretion of hexose-containing oligosaccharides can theoretically generate false positive results. To solve this problem, a threshold of 500 µg · mL−1 has been proposed for screening purposes [9]. Indeed, several negative samples, analyzed with this method, showed an isCID signal from endogenous oligosaccharides with 10-100 fold lower signals than the suggested threshold (Figure 6b).


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)

SEMI-QUANTITATIVE DETERMINATION OF [Glu3-H2O+H]+ CONCENTRATION IN A REPRESENTATIVE BATCH OF ROUTINE SAMPLES (N= 50), COMPARED TO A QUALITY CONTROL SAMPLE SPIKED AT 500 µg · mL−1 IN FSMS (A) AND ISCID (B) MODE AND 3, 12 AND 24 HOURS EXCRETION SAMPLES.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 0006: SEMI-QUANTITATIVE DETERMINATION OF [Glu3-H2O+H]+ CONCENTRATION IN A REPRESENTATIVE BATCH OF ROUTINE SAMPLES (N= 50), COMPARED TO A QUALITY CONTROL SAMPLE SPIKED AT 500 µg · mL−1 IN FSMS (A) AND ISCID (B) MODE AND 3, 12 AND 24 HOURS EXCRETION SAMPLES.
Mentions: Compared to HES, selectivity is a bigger issue for dextran because physiopathological excretion of hexose-containing oligosaccharides can theoretically generate false positive results. To solve this problem, a threshold of 500 µg · mL−1 has been proposed for screening purposes [9]. Indeed, several negative samples, analyzed with this method, showed an isCID signal from endogenous oligosaccharides with 10-100 fold lower signals than the suggested threshold (Figure 6b).

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