Document Detail


Surface-activated chemical ionization-electrospray mass spectrometry in the analysis of urinary thiodiglycolic acid.
MedLine Citation:
PMID:  23280980     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: Thiodiglycolic acid (TDGA) is a urinary metabolite of the oxazaphosphorine class of chemotherapeutics, in particular of ifosfamide. Ifosfamide metabolism generates chloroacetaldehyde (CAA), a toxic compound associated with neurotoxicity, nephrotoxicity, urotoxicity and cardiotoxicity. CAA, in turn, interacts with cellular thiol groups leading to GSH depletion, cell death and generation of thiodiglycolic acid (TDGA), as a final product. TDGA is mainly excreted in the urine. The ability to accurately measure TDGA in urine, therefore, will be a useful way of monitoring exposure to ifosfamide during chemotherapy.
METHODS: TDGA in urine samples was measured with liquid chromatography coupled to mass spectrometry (LC/MS) by means of a novel Surface-Activated Chemical Ionization-Electrospray (SACI-ESI) or a classical ESI ion source alone.
RESULTS: The SACI-ESI and ESI alone based methods for analysis of urinary TDGA were optimized and compared. A strong reduction in matrix effect together with enhanced quantification performances was obtained with the SACI-ESI when compared with ESI. In particular, an increase in quantification precision (from 85 to 95%) and accuracy (from 59 to 90%) were observed, which allowed for optimal detection of TDGA.
CONCLUSIONS: The LC/SACI-ESI-MS approach provides a very sensitive and quantitative method for the analysis of TDGA. Thanks to the enhancement in sensitivity and matrix effect reduction, the SACI-ESI source enables the use of a relatively low-cost ion-trap mass spectrometer in the analysis of this toxicity biomarker in urine. Due to these characteristics, this approach would constitute an invaluable tool in the clinical laboratory, for measuring TDGA and other toxicity related biomarkers of chemotherapy with proper sensitivity and accuracy.
Authors:
Giovanni Puccio; Paolo Brambilla; Matteo Conti; Desirée Bartolini; Douglas Noonan; Adriana Albini
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Rapid communications in mass spectrometry : RCM     Volume:  27     ISSN:  1097-0231     ISO Abbreviation:  Rapid Commun. Mass Spectrom.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-02     Completed Date:  2013-06-03     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  8802365     Medline TA:  Rapid Commun Mass Spectrom     Country:  England    
Other Details:
Languages:  eng     Pagination:  476-80     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 John Wiley & Sons, Ltd.
Affiliation:
Emmanuele Scientific Research Association, Palermo, Italy.
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MeSH Terms
Descriptor/Qualifier:
Chromatography, Liquid / methods
Humans
Reproducibility of Results
Sensitivity and Specificity
Spectrometry, Mass, Electrospray Ionization / methods*
Thioglycolates / chemistry,  metabolism,  urine*
Chemical
Reg. No./Substance:
0/Thioglycolates; 483M3RG5GW/thiodiacetic acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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