Assessment of Tear Concentrations on Therapeutic Drug Monitoring. III. Determination of Theophylline in Tears by Gas Chromatography/Mass Spectrometry with Electron Ionization Mode

Abstract

A simple and sensitive method for the quantitation of theophylline (TP) in tears and plasma developed using gas chromatography/electron-impact ionization/mass spectrometry. Tears were collected by non-invasive Schirmer method. Plasma was pipetted on a Schirmer tear test strip (cutting to 5 mm×5 mm). Then, TP was converted directly into its pentafluorobenzoyl amide derivative without the need to perform any extraction from the biological fluid absorbed on Schiemer test paper and was quantified by gas chromatography-selected ion recordings with electron ionization mode. The concentrations in tears [C]t correlated very well with those of the free form in the plasma [Cf]p and those of the total form in the plasma [Cb+f]p. The ratios between TP concentrations in tears and plasma (free and total form) were as follows: [C]t/[Cb+f]p=0.53±0.20; [C]t/[Cf]p=1.21±0.19; [Cf]p/[Cb+f]p=0.44±0.14. The ratios of [C]t/[Cb+f]p, [C]t/[Cf]p and [Cf]p/[Cb+f]p were in good agreement with the previously published data.