Measurement of phenylacetic acid in cerebrospinal fluid and plasma using combined gas chromatography/electron capture chemical ionization mass spectrometry.

Abstract

Details are presented of an ultra-sensitive gas chromatographic/mass spectrometric assay for phenylacetic acid in plasma and cerebrospinal fluid based on measurements of the relative intensities of the carboxylate anions, derived from the penta- and tetrafluorobenzyl esters under electron capture chemical ionization conditions, of unlabeled and a (13C2)-labeled internal standard. The limits of detection for the penta- and tetrafluorobenzyl esters are 0.85 and 4.0 pg respectively, and the assay is capable of measuring phenylacetic acid concentrations in samples as small as 20 microliter of CSF and plasma. The penta- and tetrafluorobenzyl esters are chromatographically separated on the gas chromatograph column, which allows for their co-injection and independent measurement from the same chromatogram.