Simultaneous Determination of Enantiomers of Furaltadone and Its Metabolite by Liquid Chromatography Tandem Mass Spectrometry: Stereoselective Pharmacokinetics, Tissue Distribution, and Antibacterial Activity

Abstract

Furaltadone and its metabolite 3-amino-5-morpholinomethyl-2-oxazolidone (AMOZ) are chiral compounds, yet their stereoselective pharmacokinetics, tissue distribution, and bioactivity remain poorly understood. This study developed and validated a sensitive liquid chromatography-tandem mass spectrometry method for simultaneously determining furaltadone and AMOZ enantiomers. Crucially, no interconversion between R- and S-furaltadone occurred in vivo or in vitro. Following oral gavage of furaltadone (20 mg/kg b.w.) in mice, furaltadone was rapidly metabolized, plasma R-furaltadone displayed higher Cmax and AUC0–24h than S-furaltadone, while, concurrently, S-AMOZ demonstrated higher Cmax and AUC0–48h. Strikingly, S-AMOZ predominated in most mouse tissues except the lungs. Pronounced stereoselectivity differences emerged in the liver (p < 0.001) and lung (p < 0.01), and were notably evident in the heart, spleen, eye, and large intestine (all p < 0.05). Significantly, R-furaltadone exhibited greater antibacterial activity in vitro. These comprehensive findings provide valuable insights into the use of furaltadone in nonfood-producing animals and inform its toxicity assessment.