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Detection of urinary markers for thiazide diuretics after oral administration of hydrochlorothiazide and altizide-relevance to doping control analysis

Koen Deventer UGent, Oscar Juan Pozo Mendoza UGent, Peter Van Eenoo UGent and Frans Delbeke UGent (2009) JOURNAL OF CHROMATOGRAPHY A. 1216(12). p.2466-2473
abstract
In sports. thiazide diuretics are used to flush out previously taken prohibited substances with forced diuresis and in sports where weight classes are involved to achieve acute weight loss. Thiazide diuretics include compounds which are very unstable and hydrolyse in aqueous media. Because information regarding the urinary detection of the hydrolysis products is limited, urinary excretion profiles for the hydrolysis product 4-aniino-6-chloro-1,3-benzenedisulphonamide were established in 6 healthy volunteers after oral administration of altizide (15 mg per tablet) and hydrochlorothiazide (25 mg per tablet). Additionally, the excretion profile of chlorothiazide, a metabolite of altizide and hydrochlorothiazide, was also determined. A quantitative liquid-chromatographic tandem mass spectrometric method to detect the 4 substances was developed and validated. The result of this work shows that altizide is eliminated within 48 h in urine whereas hydrochlorothiazide was detectable after 120 h. Chlorothiazide was determined to be a minor metabolite of altizide and hydrochlorothiazide and could be detected up to 120 h. The hydrolysis product, 4-amino-6-chloro-1.3-benzenedisulphonamide, was detectable 120 h after administration, with concentrations at least 10 times higher than the parent drug. Concentrations ranged between 41-239 and 60-287 ng/mL after altizide and hydrochlorothiazide administration, respectively. The study shows that 4-amino-6-chloro-1,3-benzenedisulphonamide is an important target compound for the long time detection of thiazide diuretics in urine. (c) 2009 Elsevier B.V. All rights reserved.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
EXCRETION, METABOLISM, PLASMA, Doping, Urine, Diuretics, Thiazides, LC-MS, TANDEM MASS-SPECTROMETRY, LIQUID-CHROMATOGRAPHY, AGENTS, PHARMACOKINETICS
journal title
JOURNAL OF CHROMATOGRAPHY A
J. Chromatogr. A
volume
1216
issue
12
pages
2466 - 2473
publisher
Elsevier Science
place of publication
PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
Web of Science type
Article
Web of Science id
000264217800033
JCR category
CHEMISTRY, ANALYTICAL
JCR impact factor
4.101 (2009)
JCR rank
4/70 (2009)
JCR quartile
1 (2009)
ISSN
0021-9673
DOI
10.1016/j.chroma.2009.01.032
language
English
UGent publication?
yes
classification
A1
id
714074
handle
http://hdl.handle.net/1854/LU-714074
date created
2009-07-06 10:00:23
date last changed
2009-07-28 15:13:56
@article{714074,
  abstract     = {In sports. thiazide diuretics are used to flush out previously taken prohibited substances with forced diuresis and in sports where weight classes are involved to achieve acute weight loss. Thiazide diuretics include compounds which are very unstable and hydrolyse in aqueous media. Because information regarding the urinary detection of the hydrolysis products is limited, urinary excretion profiles for the hydrolysis product 4-aniino-6-chloro-1,3-benzenedisulphonamide were established in 6 healthy volunteers after oral administration of altizide (15 mg per tablet) and hydrochlorothiazide (25 mg per tablet). Additionally, the excretion profile of chlorothiazide, a metabolite of altizide and hydrochlorothiazide, was also determined. A quantitative liquid-chromatographic tandem mass spectrometric method to detect the 4 substances was developed and validated. The result of this work shows that altizide is eliminated within 48 h in urine whereas hydrochlorothiazide was detectable after 120 h. Chlorothiazide was determined to be a minor metabolite of altizide and hydrochlorothiazide and could be detected up to 120 h. The hydrolysis product, 4-amino-6-chloro-1.3-benzenedisulphonamide, was detectable 120 h after administration, with concentrations at least 10 times higher than the parent drug. Concentrations ranged between 41-239 and 60-287 ng/mL after altizide and hydrochlorothiazide administration, respectively. The study shows that 4-amino-6-chloro-1,3-benzenedisulphonamide is an important target compound for the long time detection of thiazide diuretics in urine. (c) 2009 Elsevier B.V. All rights reserved.},
  author       = {Deventer, Koen and Pozo Mendoza, Oscar Juan and Van Eenoo, Peter and Delbeke, Frans},
  issn         = {0021-9673},
  journal      = {JOURNAL OF CHROMATOGRAPHY A},
  keyword      = {EXCRETION,METABOLISM,PLASMA,Doping,Urine,Diuretics,Thiazides,LC-MS,TANDEM MASS-SPECTROMETRY,LIQUID-CHROMATOGRAPHY,AGENTS,PHARMACOKINETICS},
  language     = {eng},
  number       = {12},
  pages        = {2466--2473},
  publisher    = {Elsevier Science},
  title        = {Detection of urinary markers for thiazide diuretics after oral administration of hydrochlorothiazide and altizide-relevance to doping control analysis},
  url          = {http://dx.doi.org/10.1016/j.chroma.2009.01.032},
  volume       = {1216},
  year         = {2009},
}

Chicago
Deventer, Koen, Oscar Juan Pozo Mendoza, Peter Van Eenoo, and Frans Delbeke. 2009. “Detection of Urinary Markers for Thiazide Diuretics After Oral Administration of Hydrochlorothiazide and Altizide-relevance to Doping Control Analysis.” Journal of Chromatography A 1216 (12): 2466–2473.
APA
Deventer, K., Pozo Mendoza, O. J., Van Eenoo, P., & Delbeke, F. (2009). Detection of urinary markers for thiazide diuretics after oral administration of hydrochlorothiazide and altizide-relevance to doping control analysis. JOURNAL OF CHROMATOGRAPHY A, 1216(12), 2466–2473.
Vancouver
1.
Deventer K, Pozo Mendoza OJ, Van Eenoo P, Delbeke F. Detection of urinary markers for thiazide diuretics after oral administration of hydrochlorothiazide and altizide-relevance to doping control analysis. JOURNAL OF CHROMATOGRAPHY A. PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS: Elsevier Science; 2009;1216(12):2466–73.
MLA
Deventer, Koen, Oscar Juan Pozo Mendoza, Peter Van Eenoo, et al. “Detection of Urinary Markers for Thiazide Diuretics After Oral Administration of Hydrochlorothiazide and Altizide-relevance to Doping Control Analysis.” JOURNAL OF CHROMATOGRAPHY A 1216.12 (2009): 2466–2473. Print.