title: Surface-activated chemical ionization-electrospray mass spectrometry in the analysis of urinary thiodiglycolic acid.
abstract: BACKGROUND
  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.affiliation: Emmanuele Scientific Research Association, Palermo, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Puccio
authors.forename: Paolo
authors.initials: P
authors.lastname: Brambilla
authors.forename: Matteo
authors.initials: M
authors.lastname: Conti
authors.forename: Desirée
authors.initials: D
authors.lastname: Bartolini
authors.forename: Douglas
authors.initials: D
authors.lastname: Noonan
authors.forename: Adriana
authors.initials: A
authors.lastname: Albini
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods; D006801:Humans; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013864:Thioglycolates / Q000737:chemistry / Q000378:metabolism / Q000652:urine*
chemical_list: D013864:Thioglycolates; C010518:thiodiacetic acid