The matrix effect in particle beam liquid chromatography/mass spectrometry and reliable quantification by isotope dilution.

The transport efficiency of the particle beam liquid chromatography/mass spectrometer interface is influenced by analyte concentration contributing to a widely reported non-linearity. In this work, coeluting, isotope-labeled internal standards were investigated as 'carriers' to improve the transport efficiency and linearity. Three styrene metabolites--mandelic, phenylglyoxylic and hippuric acids--and their pentadeutero analogs were separated by reversed-phase liquid chromatography (LC) with an ammonium acetate-acetonitrile mobile phase. Selected positive ions produced by electron ionization were monitored to generate particle beam LC/MS calibration curves. The present study demonstrates that particle beam LC/MS not only is non-linear, but also is subject to a matrix effect presumably by the same mechanism responsible for non-linearity. Coeluting, isotope-labeled internal standards were ineffective at linearizing the particle beam liquid chromatograph/mass spectrometer detector response. Isotope dilution quantification, however, compensates for variable transport efficiencies, linearizes calibration and compensates for the matrix effect, affording reliable quantification of the styrene metabolites.