QUANTITATIVE MEASUREMENT OF ZACOPRIDE IN HUMAN PLASMA AND URINE BY COMBINED GAS-CHROMATOGRAPHY NEGATIVE-ION CHEMICAL-IONIZATION MASS-SPECTROMETRY

A highly sensitive and specific assay was developed for routine analysis of zacopride at the femtomole level in human plasma and urine. Zacopride and the deuterated internal standard [(H-2(3))zacopride] were measured by gas chromatography/negative ion chemical ionization mass spectrometry with methane as the reagent gas. A multiple-step liquid-liquid extraction procedure was used to isolate the two compounds of interest from complex biological matrices. Zacopride was converted to the fluorinated derivative with pentafluoropropionic anhydride. The mass spectrometer was tuned to monitor the very intense [M - HF](-) ion at m/z 435 which was generated into the ion source by a dissociative capture process. This assay was performed with 1 mi of plasma or 0.2 ml of urine, and the quantification limit of the method was calculated as 10 pg ml(-1) using a suitable statistical test. The very low relative standard deviation and mean percentage error values calculated during the within-day or between-day repeatability assays have clearly demonstrated the ruggedness of the technique for the routine quantitative measurement of zacopride in plasma and urine. Some preliminary results on the pharmacokinetics of this potent drug are presented to illustrate the applicability of this new powerful gas chromatographic/mass spectrometric method.