title: Pyroglutamate (5-oxoproline) measured with hydrophilic interaction chromatography (HILIC) tandem mass spectrometry in acutely ill patients.
abstract: BACKGROUND
  Pyroglutamic acid (PGA) is challenging to quantify in plasma and is a rare cause of metabolic acidosis that is associated with inherited disorders or acquired after exposure to drugs.
  
  
  METHODS
  We developed a hydrophilic interaction liquid chromatography tandem mass spectrometry method with a short analysis time. We established a reference interval and then measured PGA in acutely ill patients to investigate associations with clinical, pharmaceutical and laboratory parameters.
  
  
  RESULTS
  The assay limit of the blank was 0.14μmol/L and was linear to 5000μmol/L with good precision. In-source formation of PGA from glutamate and glutamine was avoided by chromatographic separation. The PGA in controls had a reference interval of 22.6 to 47.8μmol/L. The median PGA concentration in acutely ill patients was similar (P=0.21), but 18 individuals were above the reference interval with concentrations up to 250μmol/L. We detected an association between PGA concentration and antibiotic and acetaminophen administration as well as renal impairment and severity of illness. Elevations of PGA in this unselected cohort were small compared to those reported in patients with pyroglutamic acidosis.
  
  
  CONCLUSIONS
  The method is suitable for routine clinical use. We confirmed several expected associations with PGA in an acutely ill population.
authors.affiliation: Department of Chemical Pathology, Pathology Queensland, Queensland Health, Brisbane, Australia; University of Queensland, School of Medicine, Brisbane, Australia. Electronic address: carel.pretorius@health.qld.gov.au.
authors.forename: Carel J
authors.initials: CJ
authors.lastname: Pretorius
authors.affiliation: University of Queensland, School of Medicine, Brisbane, Australia; Burns Trauma & Critical Care Research Centre, University of Queensland, Brisbane, Australia; Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia; Joint Health Command, Australian Defence Force, Canberra, Australia.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Reade
authors.affiliation: Department of Chemical Pathology, Pathology Queensland, Queensland Health, Brisbane, Australia.
authors.forename: Chris
authors.initials: C
authors.lastname: Warnholtz
authors.affiliation: Department of Chemical Pathology, Pathology Queensland, Queensland Health, Brisbane, Australia.
authors.forename: Brett
authors.initials: B
authors.lastname: McWhinney
authors.affiliation: University of Queensland, School of Medicine, Brisbane, Australia.
authors.forename: Meng Mei
authors.initials: MM
authors.lastname: Phua
authors.affiliation: University of Queensland, School of Medicine, Brisbane, Australia; Burns Trauma & Critical Care Research Centre, University of Queensland, Brisbane, Australia; Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
authors.affiliation: Department of Chemical Pathology, Pathology Queensland, Queensland Health, Brisbane, Australia.
authors.forename: Jacobus P J
authors.initials: JPJ
authors.lastname: Ungerer
mesh_terms: D000138:Acidosis / Q000097:blood* / Q000175:diagnosis; D000208:Acute Disease; D002853:Chromatography, Liquid / Q000379:methods; D015331:Cohort Studies; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D057230:Limit of Detection; D011761:Pyrrolidonecarboxylic Acid / Q000097:blood*; D012015:Reference Standards; D012720:Severity of Illness Index; D053719:Tandem Mass Spectrometry / Q000379:methods* / Q000592:standards
chemical_list: D011761:Pyrrolidonecarboxylic Acid
keywords: Anion gap; Hydrophilic interaction chromatography; Mass spectrometry; Metabolic acidosis; Oxoproline; Pyroglutamate