Simultaneous determination of ethylene glycol and its major toxic metabolite, glycolic acid, in serum by gas chromatography

Abstract

We developed a gas-chromatographic procedure for the simultaneous determination of ethylene glycol (EG) and its major toxic metabolite, glycolic acid (GA), suitable for clinical use in instances of EG intoxication. After serum protein precipitation with acetonitrile (containing internal standard), the supernate is treated with 2,2-dimethoxypropane (containing dimethylformamide) to remove water, and the volume is then reduced by evaporation to <100 microL of dimethylformamide (but not to dryness). After trimethylsilyl derivatization, the resulting derivatives are analyzed by capillary column gas chromatography. Only 100 microL of serum is required and the entire determination, including calibrators and controls, takes <2 h. The method gives a linear response to at least 10 g/L EG and 5 g/L GA and has a limit of detection <10 mg/L. Intraassay CV is < or = 2.8% for EG (100 and 1000 mg/L) and GA (100 and 500 mg/L); between-day CV is < or = 6.5%. The absolute recovery from serum was 91% for EG and 77-82% for GA (200 and 2000 mg/L each). Relative to calibrators prepared bovine serum albumin (70 g/L), the recovery was 99-104% for EG (100 - 5000 mg/L) and 95-105% for GA (50 - 2500 mg/L). No clinically important interference was detected for >60 exogenous or endogenous compounds and drugs.

Use of a Rapid Ethylene Glycol Assay: a 4-Year Retrospective Study at an Academic Medical Center

“…The patient was unable to provide complete ingestion history even after recovery. Laboratory abnormalities at time of admission included serum anion gap of 29 (reference range, [8][9][10][11][12][13][14][15][16][17][18] and whole blood lactic acid of 25 mEq/L (reference range, 0.5-2.2). Examination of urine did not reveal oxalate crystals.…”

“…An inebriated or somnolent patient often cannot provide a reliable history, and the differential diagnosis of non-specific symptoms and signs such as altered mental status, elevated anion gap, or elevated osmolal gap is extensive [3,4]. Gas chromatography (GC), with or without mass spectrometry (GC/MS), can be used for accurate and specific quantitative measurement of EG in serum/plasma and is the current gold standard diagnostic method [3,4,[7][8][9]. Although GC is widely used for measurement of EG in clinical samples, GC/MS has greater specificity and can avoid interference of EG measurement by 2,3-butanediol (found in serum of some alcoholics) [10] or analytes present at high concentrations in rare inborn errors of metabolism (e.g., propionic acid in methylmalonic acidemia) [11].…”

Successful therapy of paediatric ethylene glycol poisoning: a case report and annual survey by a regional poison centre

“…Several chromatographic methods for determination of ethylene glycol in serum have been published. Gold standard method for glycol identification is gas chromatography with mass selective detection (GC/MS) (7,8). A robust and rapid method for quantitative serum analysis of more than 15 glycols and glycol ethers using flame ionisation detection (GC/FID) was reported more recently (9,3).…”

Détermination de la concentration sérique du formiate et du glycolate par spectroscopie RMN1H : une technologie nouvelle applicable au diagnostic tardif des intoxications par le méthanol et l'éthylène glycol

“…La plupart des méthodes d'analyse de l'acide glycolique utilisent la CPG (16) mais aussi la chromatographic ionique (19). Certaines associent la mesure simultanée de 1'ethylene glycol et de l'acide glycolique (20). Un pool de sérums témoins a été supplémenté (sérums de calibration, CHR Vannes) en formiate ou en glycolate afin de réaliser des gammes de concentrations : 0, 2, 10, 20 et 40 mmol/l.…”