Gas--liquid chromatographic determination of toloxatone in human plasma. Routine analysis of a wide range of drug concentrations using a nitrogen-selective detector.

A selective and sensitive gas--liquid chromatographic (GLC) method has been developed for the measurement of toloxatone at therapeutic concentrations in plasma. The technique is based on a single extraction from plasma at pH 10, the preparation of a trimethylsilyl derivative and detection by a nitrogen-selective detector. The traditional calibration curve, peak-area ratio of toloxatone to internal standard versus toloxatone plasma concentration, was slightly concave for the wide concentration considered (10-3000 ng/ml). As a consequence, the linear least-squares regression analysis gave a negative intercept on the gamma-axis which affected quantitation accuracy of low plasma concentration values. A calibration method taking into consideration the non-linearity of the calibration curve is proposed. The characteristics of the detector were examined in order to analyse response linearity and sensitivity. A linear relationship was found between background current and detector sensitivity.