Metabolism and Disposition of Siponimod, a Novel Selective S1P/S1P Agonist, in Healthy Volunteers and In Vitro Identification of Human Cytochrome P450 Enzymes Involved in Its Oxidative Metabolism.

Siponimod, a next-generation selective sphingosine-1-phosphate receptor modulator, is currently being investigated for the treatment of secondary progressive multiple sclerosis. We investigated the absorption, distribution, metabolism, and excretion (ADME) of a single 10-mg oral dose of [C]siponimod in four healthy men. Mass balance, blood and plasma radioactivity, and plasma siponimod concentrations were measured.

Cytostar-T plates--a valid alternative for microplate scintillation counting of low radioactivity in combination with high-performance liquid chromatography in drug metabolism studies?

The determination of radioactivity from metabolite patterns in ADME studies in a low radioactivity/residue situation is a very challenging process requiring special technologies. The recently introduced TopCount technology uses LumaPlates for the collection of the column effluent after HPLC separation to subsequently determine radioactivity for the generation of the metabolite profile. Samples from drug metabolism studies were used to compare the performance of the widely used LumaPlates with Cytostar-T plates regarding sensitivity and recovery of metabolites for structure elucidation by MS.