Journal
DRUG TESTING AND ANALYSIS
Volume 11, Issue 7, Pages 1094-1108Publisher
WILEY
DOI: 10.1002/dta.2584
Keywords
biomarker; clinical toxicology; ethylene glycol; glucuronide; poisoning
Funding
- Augustinus Fonden
- Brodrene Hartmanns Fond
- Lundbeckfonden
- Marie Pedersen og Jensine Pedersens Legat
- Lundbeck Foundation
- A.P. Moller Foundation for the Advancement of Medical Science
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In the search for improved laboratory methods for the diagnosis of ethylene glycol poisoning, the in vivo formation of a glucuronide metabolite of ethylene glycol was hypothesized. Chemically pure standards of the beta-O-glucuronide of ethylene glycol (EG-GLUC) and a deuterated analog (d(4)-EG-GLUC) were synthesized. A high-performance liquid chromatography and tandem mass spectrometry method for determination of EG-GLUC in serum after ultrafiltration was validated. Inter-assay precision (%RSD) was 3.9% to 15.1% and inter-assay %bias was -2.8% to 12.2%. The measuring range was 2-100 mu mol/L (0.48-24 mg/L). Specificity testing showed no endogenous amounts in routine clinical samples (n = 40). The method was used to analyze authentic, clinical serum samples (n = 31) from patients intoxicated with ethylene glycol. EG-GLUC was quantified in 15 of these samples, with a mean concentration of 6.5 mu mol/L (1.6 mg/L), ranging from 2.3 to 15.6 mu mol/L (0.55 to 3.7 mg/L). In five samples, EG-GLUC was detected below the limit of quantification (2 mu mol/L) and it was below the limit of detection in 11 samples (1 mu mol/L). Compared to the millimolar concentrations of ethylene glycol present in blood after intoxications and potentially available for conjugation, the concentrations of EG-GLUC found in clinical serum samples are very low, but comparable to concentrations of ethyl glucuronide after medium dose ethanol intake. In theory, EG-GLUC has a potential value as a biomarker for ethylene glycol intake, but the pharmacokinetic properties, in vivo/vitro stability and the biosynthetic pathways of EG-GLUC must be further studied in a larger number of patients and other biological matrices.
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