SIMULTANEOUS DETERMINATION OF MOEXIPRIL AND MOEXIPRILAT, ITS ACTIVE METABOLITE, IN HUMAN PLASMA BY GAS-CHROMATOGRAPHY NEGATIVE-ION CHEMICAL-IONIZATION MASS-SPECTROMETRY

A sensitive and selective method for the simultaneous determination of moexipril and moexiprilat, its active metabolite, in human plasma is described using quinapril and quinaprilat as internal standards. The a nalytes are isolated from human plasma by means of Bond Elut C-18 cart ridges, methylated with diazomethane, purified by acid-base partitioni ng and converted to the corresponding trifluoroacetamides using triflu oroacetic anhydride. Moexipril and moexiprilat were analysed by gas ch romatography-negative-ion chemical ionization mass spectrometry (GC-NI CI-MS) at the fragment ions mit 302 and mit 288, respectively. The low er limit of quantitation both for moexipril and moexiprilat is 0.5 ng/ ml of human plasma. Linear calibration curves are obtained over the co ncentration range 0.5-300 ng/ml of human plasma. In any case the impre cision and the inaccuracy are < 15%. The present method has been succe ssfully applied to various pharmacokinetic studies in human subjects a nd patients.