Ovine Metabolism of Lithogenic Sapogenins. Synthesis of [2,2,4,4-<sup>2</sup>H<sub>4</sub>]Sarsasapogenone, [2,2,4,4-<sup>2</sup>H<sub>4</sub>]Sarsasapogenin, and [2,2,4,4-<sup>2</sup>H<sub>4</sub>]Episarsasapogenin and Evaluation of Deuterium Retention in a Sheep-Dosing Trial LoaderJared I. WilkinsAlistair L. FlåøyenArne RysteEvrind HoveKnut 2003 The suitability of [2,2,4,4-<sup>2</sup>H<sub>4</sub>]sarsasapogenone (<b>1b</b>), [2,2,4,4-<sup>2</sup>H<sub>4</sub>]sarsasapogenin (<b>2b</b>), and [2,2,4,4-<sup>2</sup>H<sub>4</sub>]episarsasapogenin (<b>3b</b>) as isotopically labeled dosing substrates to determine the levels of free and conjugated sapogenins present in feces from sheep grazing saponin-containing plants implicated in the development of ovine heptagenous photosentization diseases was investigated. A 1:4 mixture of [2,2,4,4-<sup>2</sup>H<sub>4</sub>]sarsasapogenin (<b>2b</b>) and [2,2,4,4-<sup>2</sup>H<sub>4</sub>]episarsasapogenin (<b>3b</b>), obtained by reduction of [2,2,4,4-<sup>2</sup>H<sub>4</sub>]sarsasapogenone (<b>1b</b>), was found to retain 94% of incorporated deuterium, when dosed to one sheep. The recovery of the dosed mixture of genins <b>2b</b> and <b>3b</b> was calculated to be 85%. Considerable loss of deuterium and a lower recovery of genin material were observed when [2,2,4,4-<sup>2</sup>H<sub>4</sub>]sarsasapogenone (<b>1b</b>) was dosed. Keywords: Deuterated sapogenins; dosing trial; sheep; fecal material; <i>Narthecium ossifragum</i>; episarsasapogenin; sarsasapogenin; sarsasapogenone