Sensitive electron-capture GLC determination of metoclopramide in biological fluids

A highly sensitive and specific electron-capture GLC assay capable of detecting picogram quantities of metoclopramide, a procaine derivative, in biological fluids was developed. This assay consisted of extracting metoclopramide from an alkalinized aqueous layer into benzene. A portion of the organic phase was derivatized with heptafluorobutyric anhydride. Quantitative estimation of the derivative was accomplished by adding diazepam, the internal standard, in bezene (750 ng/ml). A calibration curve was prepared for the plasma extracts. Linearity was observed in the range studied (91-825 ng/ml). No interference from endogenous substances was observed. The minimum detectable amount was 1 pg/injection. The structure of the derivative was confirmed by electron-impact and chemical-ionization mass spectrometry. The applicability of this method was shown by a preliminary study of the elimination kinetics of metoclopramide in rats after a 10-mg/kg iv dose.