Development of a liquid chromatography-mass spectrometry method for the determination of the neurotoxic quinolinic acid in human serum

摘要

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 muL 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.Conclusion: 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 foi clinical laboratory routine.