Determination of metoclopramide in human plasma by LC-ESI-MS and its application to bioequivalance studies

An LC-MS method for the determination of metoclopramide in human plasma was developed and validated. Sample preparation involved extraction with ethyl acetate. Chromatographic separation was performed on a Thermo Hypersil-Hypurity C-18 (150 mm x 2.1 mm, 5 mu m) with the mobile phase consisting of 40 mM ammonium acetate-methanol-acetonitrile. A single-quadrupole mass spectrometer with an electrospray interface was operated in the selected-ion monitoring mode to detect the [M+H](+) ions at m/z 300 for metoclopramide and at m/z 384 for the internal standard (prazosin). The method was validated over 0.78-50.00 ng mL(-1) for metoclopramide. The recovery was 67.8-83.1%, and the limit of quantitation (LOQ) detection was 0.78 ng mL(-1) for metoclopramide. The intra- and inter-day precision of the method at three concentrations was 5.0-13.6% with accuracy of 99.2-104.0%. Stability of compounds was established in a battery of stability studies. The method was successfully applied to bioequivalence studies of metoclopramide hydrochloride tablets to obtain the pharmacokinetic parameters. (c) 2010 Elsevier B.V. All rights reserved.