PROBLEMATIC ISSUES OF STUDYING THE PHARMACOKINETICS OF TRIMEBUTINE

Abstract

Determination of pharmacokinetics of actively metabolized drugs is a key problem of assessing their bioavailability. Taking trimebutine as an example, possible solutions to this problem are presented in the work. In the experiment in vitro at the original model solution metabolic liver homogenate was determined by the concentration of the active metabolite of trimebutine concentration as the difference in the solution before and after incubation. By using the technology of detecting LS-MS mass-spectrum basic ion trimebutine (388 m/z) and mass-spectrum of the main metabolite of trimebutine ion (370.3 m/z) were identified. The calibration dependence (correlation coefficient 0.988), which was used to determine the main metabolite of trimebutine, was created on its ion mass-spectrum with 370.3 m/z. There was described a new method for the quantitative determination of the major metabolite of trimebutine - N-monodesmethyl trimebutine using liquid chromatography-mass spectrometry, which allowed to assess adequately on rabbits the pharmacokinetics of various forms of the medication in the experiment.