Quantification of quinolinic acid in rat brain, whole blood, and plasma by gas chromatography and negative chemical ionization mass spectrometry: Effects of systemic l-tryptophan administration on brain and blood quinolinic acid concentrations

✍ Scribed by Melvyn P. Heyes; Sanford P. Markey

• Publisher: Elsevier Science
• Year: 1988
• Tongue: English
• Weight: 935 KB
• Volume: 174
• Category: Article
• ISSN: 0003-2697
• DOI: 10.1016/0003-2697(88)90556-8

✦ Synopsis

A gas chromatography/mass spectrometry assay is described to quantify the endogenous neurotoxin quinolinic acid (QUIN) in brain, whole blood, and plasma. High specificity and high sensitivity were obtained by using negative chemical ionization and accuracy was achieved by using ['80]QUlN as internal standard. Neutralized perchloric acid extracts were washed with chloroform, applied to Dowex 1X8 (formate form), and eluted with 6 M formic acid. After lyophilization, QUIN and [ "O]QUlN were esterified with hexafluoroisopropanol (to mass 467 and 47 1, respectively) using trifluoroacetylimidazole as catalyst. The esters were extracted into heptane and injected onto a gas chromatograph, DB-5 capillary column. QUIN and ['80]QUlN were quantified by selected ion monitoring of QUIN-specific anion currents from the molecular anions (m/z 467 and 47 1, respectively) and a specific anion fragment (m/z 3 16 from QUIN and m/z 320 from ['*O]QUlN). Minimum sensitivity was 3 fmol, intraassay variability was 3.2%, and interassay variability was 8.1%. QUIN concentrations in frontal cortex from over 200 rats ranged from 20 to 180 fmol/mg wet wt. Two hours after systemic L-tryptophan (L-Trp; 0.370 mmol/kg) administration, QUIN increased in whole blood 134.8-fold and in plasma. 74.3-fold. In frontal cortex, increases in QUIN (22.6-fold, corrected for QUIN in blood) exceeded increases in cortical L-Trp (2.54-fold). 5-HT (I .35-fold), and 5-HIAA (I .74-fold). These studies demonstrate that QUIN is present in brain and is sensitive to the availability of systemic L-Trp.