A METHOD USING A LIQUID-CHROMATOGRAPHIC ELECTROSPRAY MASS-SPECTROMETRIC ASSAY FOR THE DETERMINATION OF ANTIMIGRAINE COMPOUNDS - PRELIMINARYPHARMACOKINETICS OF MDL-74,721, SUMATRIPTAN AND NARATRIPTAN, IN RABBIT

MDL 74,721 (I), sumatriptan(II) and naratriptan(III) are new 5-HT1-lik e agonists that have potential as a novel treatment for migraine. Liqu id chromatographic-electrospray-mass spectrometric (LC-ESI-MS) assays have been developed to compare the pharmacokinetics of these three ant imigraine compounds. The concentration of each parent drug was determi ned using a solid-phase extraction method and LC-ESI-MS analysis demon strating the high sensitivity and specificity of the methods down to s ubnanogram levels in rabbit plasma samples, Pharmacokinetic parameters evaluated after administration of single intravenous and oral doses w ere very similar and the ANOVA analysis did not show any statistically significant differences for t(1/2), C-max, V or AUC (normalised). The pharmacokinetic parameters showed short t(1/2,) (range 1.14-1.9 h) ei ther after intravenous (iv) or oral (po) administration and high total body clearance (CL) after the po dose both probably due to extensive and rapid metabolism of the parent drugs as suggested by the low value s for bioavailability (range 13.4-22.8%,). (C) 1997 Elsevier Science B .V.