Assessment of drug concentrations in tears in therapeutic drug monitoring: I. Determination of valproic acid in tears by gas chromatography/mass spectrometry with EC/NCI mode.

A rapid and sensitive method for the quantitation of valproic acid in tears has been developed using gas chromatography/electron capture negative chemical ionization/mass spectrometry. Valproic acid was converted directly into its pentafluorobenzyl ester derivative without the need to perform any extraction from the biologic fluid. 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 valproic acid concentrations in tears and plasma were as follows: [C]t/]Cb+f]p = 0.10 ± 0.02; [C]t/[Cf]p = 0.57 ± 0.11. Ratios of [C]t/[Cb+f]p were in good agreement with previously published data.