title: Development of a liquid chromatography-mass spectrometry method for the determination of the neurotoxic quinolinic acid in human serum.
abstract: BACKGROUND
  Quinolinic acid (QA) is thought to be one of the most important metabolites of the kynurenine pathway with the highest biological activity in apoptotic responses and neurodegenerative diseases. The determination of QA might be of clinical relevance in different patient groups, but currently, only a few laborious methods with high levels of sample volume consumption are available.
  
  
  METHODS
  We developed and validated a simple liquid chromatography-tandem mass spectrometric (LC-tandem MS) method for the determination of QA in human serum with low sample volume requirements.
  
  
  RESULTS
  The presented method provides high sample throughput with 25 μL aliquots and works in the positive electrospray ionization (ESI) mode. A commercially available QA-d3 was used as internal standard. Specific transitions for QA and QA-d3 were m/z 280→m/z 78 and m/z 283→m/z 81, respectively. The intra- and inter-assay coefficients of variation (CVs) were all below 10%. Applying this method, in 50 healthy humans a mean serum concentration of QA of 350±167 nmol/L (mean±SD) was determined.
  
  
  CONCLUSIONS
  The described method is suitable for large clinical trials, which is of potential clinical importance to elucidate the function of QA and its relationship to different disease patterns and may be applicable for clinical laboratory routine.
authors: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria. Electronic address: andreas.meinitzer@klinikum-graz.at.
authors: Andreas
authors: A
authors: Meinitzer
authors: Department of Cardiology, Medical University of Graz, Graz, Austria; Specialist Clinic for Rehabilitation PV Bad Aussee, Bad Aussee, Austria.
authors: Andreas
authors: A
authors: Tomaschitz
authors: Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria.
authors: Stefan
authors: S
authors: Pilz
authors: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors: Manfred
authors: M
authors: Truber
authors: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors: Gabriele
authors: G
authors: Zechner
authors: Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria.
authors: Martin
authors: M
authors: Gaksch
authors: Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria.
authors: Barbara
authors: B
authors: Prietl
authors: Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria.
authors: Gerlies
authors: G
authors: Treiber
authors: Division of Surgical Research, Department of Surgery, Medical University of Graz, Graz, Austria.
authors: Michaela
authors: M
authors: Schwarz
authors: Department of Psychiatry, Medical University of Graz, Graz, Austria.
authors: Andreas
authors: A
authors: Baranyi
mesh_terms: D000328:Adult; D053000:Analytic Sample Preparation Methods; D001774:Blood Chemical Analysis / Q000379:methods*; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D057230:Limit of Detection; D008297:Male; D009498:Neurotoxins / Q000097:blood* / Q000737:chemistry; D011786:Quality Control; D017378:Quinolinic Acid / Q000097:blood* / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D009498:Neurotoxins; D017378:Quinolinic Acid
keywords: Kynurenin pathway; Mass spectrometry; Quinolinic acid