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Specific screening method for dextran and hydroxyethyl starch in human urine by size exclusion chromatography-in-source collision-induced dissociation-time-of-flight mass spectrometry

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Abstract
The use of plasma volume expanders (PVE), such as dextran (DEX) and hydroxyethyl starch (HES), is prohibited in sports. DEX is a naturally occurring glucose polymer, whereas HES is synthetically produced from amylopectin starch by substitution with hydroxyethyl groups. In doping control, the commonly applied enzymatic and colorimetric screening methods are lacking adequate specificity for DEX and HES. Also, gas chromatographic-mass spectrometic (GC-MS) screening methods have specificity issues with DEX. In addition, due to the nature of the target compounds, time-consuming derivatisation steps are required in GC-MS. Based on the high molecular weight of carbohydrate polymers excreted in urine after administration of DEX and HES, a screening method was developed involving size exclusion chromatography (SEC) combined with time-of-flight mass spectrometry (TOFMS). By using solely a SEC guard column as an analytical column allowed sufficient chromatographic resolution in a minimal amount of time and with reasonable repeatability (average RSD of 10%). Detector response was linear throughout the measurement range with R (2) > 0.99 for both analytes. Limits of detection were 100 and 250 mu g mL(-1) for DEX and HES, respectively. Ion suppression was found to be 52% at maximum. In-source collision-induced dissociation (ISCID) was used to produce characteristic fragments at a mass accuracy better than 2 mDa. The specificity of the SEC-ISCID-TOFMS method was demonstrated with 120 PVE negative doping control samples analyzed in parallel with a routine GC-MS screening method. In addition, seven urine samples from diabetic athletes, causing interpretation problems in routine GC-MS, showed here a definitely negative profile.
Keywords
Size exclusion chromatography, Screening, Hydroxyethyl starch, Dextran, Time-of-flight mass spectrometry, PLASMA-VOLUME EXPANDERS, HEALTHY-VOLUNTEERS, PHARMACOKINETICS, EXCRETION, INFUSION, TOLERABILITY, 6-PERCENT

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Citation

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Chicago
Kolmonen, Marjo, Antti Leinonen, Tiia Kuuranne, Anna Pelander, Koen Deventer, and Ilkka Ojanperä. 2011. “Specific Screening Method for Dextran and Hydroxyethyl Starch in Human Urine by Size Exclusion Chromatography-in-source Collision-induced Dissociation-time-of-flight Mass Spectrometry.” Analytical and Bioanalytical Chemistry 401 (2): 563–571.
APA
Kolmonen, Marjo, Leinonen, A., Kuuranne, T., Pelander, A., Deventer, K., & Ojanperä, I. (2011). Specific screening method for dextran and hydroxyethyl starch in human urine by size exclusion chromatography-in-source collision-induced dissociation-time-of-flight mass spectrometry. ANALYTICAL AND BIOANALYTICAL CHEMISTRY, 401(2), 563–571.
Vancouver
1.
Kolmonen M, Leinonen A, Kuuranne T, Pelander A, Deventer K, Ojanperä I. Specific screening method for dextran and hydroxyethyl starch in human urine by size exclusion chromatography-in-source collision-induced dissociation-time-of-flight mass spectrometry. ANALYTICAL AND BIOANALYTICAL CHEMISTRY. 2011;401(2):563–71.
MLA
Kolmonen, Marjo, Antti Leinonen, Tiia Kuuranne, et al. “Specific Screening Method for Dextran and Hydroxyethyl Starch in Human Urine by Size Exclusion Chromatography-in-source Collision-induced Dissociation-time-of-flight Mass Spectrometry.” ANALYTICAL AND BIOANALYTICAL CHEMISTRY 401.2 (2011): 563–571. Print.
@article{2045137,
  abstract     = {The use of plasma volume expanders (PVE), such as dextran (DEX) and hydroxyethyl starch (HES), is prohibited in sports. DEX is a naturally occurring glucose polymer, whereas HES is synthetically produced from amylopectin starch by substitution with hydroxyethyl groups. In doping control, the commonly applied enzymatic and colorimetric screening methods are lacking adequate specificity for DEX and HES. Also, gas chromatographic-mass spectrometic (GC-MS) screening methods have specificity issues with DEX. In addition, due to the nature of the target compounds, time-consuming derivatisation steps are required in GC-MS. Based on the high molecular weight of carbohydrate polymers excreted in urine after administration of DEX and HES, a screening method was developed involving size exclusion chromatography (SEC) combined with time-of-flight mass spectrometry (TOFMS). By using solely a SEC guard column as an analytical column allowed sufficient chromatographic resolution in a minimal amount of time and with reasonable repeatability (average RSD of 10\%). Detector response was linear throughout the measurement range with R (2) {\textrangle} 0.99 for both analytes. Limits of detection were 100 and 250 mu g mL(-1) for DEX and HES, respectively. Ion suppression was found to be 52\% at maximum. In-source collision-induced dissociation (ISCID) was used to produce characteristic fragments at a mass accuracy better than 2 mDa. The specificity of the SEC-ISCID-TOFMS method was demonstrated with 120 PVE negative doping control samples analyzed in parallel with a routine GC-MS screening method. In addition, seven urine samples from diabetic athletes, causing interpretation problems in routine GC-MS, showed here a definitely negative profile.},
  author       = {Kolmonen, Marjo and Leinonen, Antti and Kuuranne, Tiia and Pelander, Anna and Deventer, Koen and Ojanper{\"a}, Ilkka},
  issn         = {1618-2642},
  journal      = {ANALYTICAL AND BIOANALYTICAL CHEMISTRY},
  keyword      = {Size exclusion chromatography,Screening,Hydroxyethyl starch,Dextran,Time-of-flight mass spectrometry,PLASMA-VOLUME EXPANDERS,HEALTHY-VOLUNTEERS,PHARMACOKINETICS,EXCRETION,INFUSION,TOLERABILITY,6-PERCENT},
  language     = {eng},
  number       = {2},
  pages        = {563--571},
  title        = {Specific screening method for dextran and hydroxyethyl starch in human urine by size exclusion chromatography-in-source collision-induced dissociation-time-of-flight mass spectrometry},
  url          = {http://dx.doi.org/10.1007/s00216-011-4838-1},
  volume       = {401},
  year         = {2011},
}

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