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 acrid in tear s has been developed using gas chromatography/electron capture negative che mical ionization/mass spectrometry. Valproic acid was converted directly in to its pentafluorobenzyl ester derivative without the need to perform any e xtraction from the biologic fluid. The concentrations in tears [C]t correla ted 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 conc entrations in tears and plasma were as follows: [C]t/[Cb+f]p = 0.10 +/- 0.0 2; [C]t/[Cf]p = 0.57 +/- 0.11. Ratios of [C]t/[Cb+f]p were in good agreemen t with previously published data.