Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5137812 | Journal of Pharmaceutical and Biomedical Analysis | 2017 | 16 Pages |
Abstract
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 1.3-250 μg mLâ1, with adequate accuracy (96.4-107.8%) and precision (12.3%). LOQ equaled 1.3 μg mLâ1 for paracetamol and 4.9 μg mLâ1 for 5-oxoproline.
Related Topics
Physical Sciences and Engineering
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Authors
TomáÅ¡ Hložek, TomáÅ¡ KÅÞek, Petr Tůma, Miroslava Bursová, Pavel Coufal, RadomÃr Äabala,