High anion gap metabolic acidosis frequently complicates acute paracetamol overdose and is generally attributed to lactic acidosis or compromised hepatic function. However, metabolic acidosis can also be caused by organic acid 5-oxoproline (pyroglutamic acid). Paracetamol's toxic intermediate, N-acetyl-p-benzoquinoneimine irreversibly binds to glutathione and its depletion leads to subsequent disruption of the gamma glutamyl cycle and an excessive 5-oxoproline generation. This is undoubtedly an underdiagnosed condition because measurement of serum 5-oxoproline level is not readily available. A simple, cost effective, and fast capillary electrophoresis method with diode array detection (DAD) for simultaneous measurement of both paracetamol (acetaminophen) and 5-oxoproline in serum was developed and validated. This method is highly suitable for clinical toxicology laboratory diagnostic, allowing rapid quantification of acidosis inducing organic acid 5-oxoproline present in cases of paracetamol overdose. The calibration dependence of the method was proved to be linear in the range of 1.3-250μgmL-1, with adequate accuracy (96.4-107.8%) and precision (12.3%). LOQ equaled 1.3μgmL-1for paracetamol and 4.9μgmL-1for 5-oxoproline.

Charles University 3rd Faculty of Medicine Department of Biochemistry Cell and Molecular Biology Ruská 87 100 00 Prague 10 Czech Republic

Charles University and General University Hospital 1st Faculty of Medicine Institute of Forensic Medicine and Toxicology Ke Karlovu 2 121 08 Prague 2 Czech Republic

Charles University Faculty of Science Department of Analytical Chemistry Albertov 6 128 43 Prague 2 Czech Republic

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