A method using a liquid chromatographic electrospray mass spectrometric assay for the determination of antimigraine compounds: Preliminary pharmacokinetics of MDL 74,721, sumatriptan and naratriptan, in rabbit

MDL 74,721 (I), sumatriptan(II) and naratriptan(III) are new 5-HT1-like agonists that have potential as a novel treatment for migraine. Liquid chromatographic-electrospray-mass spectrometric (LC-ESI-MS) assays have been developed to compare the pharmacokinetics of these three antimigraine compounds. The concentration of each parent drug was determined using a solid-phase extraction method and LC-ESI-MS analysis demonstrating the high sensitivity and specificity of the methods down to subnanogram levels in rabbit plasma samples, Pharmacokinetic parameters evaluated after administration of single intravenous and oral doses were 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) either 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 values for bioavailability (range 13.4-22.8%,). (C) 1997 Elsevier Science B.V.