Degradation Pathway of a Taxane Derivative DS80100717 Drug Substance and Drug Product

Abstract

The degradation pathway of a taxane derivative and anticancer agent, DS80100717, was investigated. Several degradants were generated under acidic, basic, and oxidative stress conditions in solution. The chemical structures of eight degradants of DS80100717 were elucidated using MS and NMR. The major degradant of the DS80100717 drug substance derived by heating in solid-state was the N-oxide form via oxidation and C2′-epimer of the side chain via acid hydrolysis. We proposed previously unreported degradation pathways of DS80100717 with taxane derivatives such as paclitaxel, docetaxel, and cabazitaxel.

Stability study of concentrate-solvent mixture & infusion solutions of Jevtana® cabazitaxel for extended multi-dosing

“…[8][9][10][11] A thorough degradation study with another cabazitaxel taxane derivate DS80100717 has also been conducted. 12 The stability in the form of concentration measurement for infusion solution stored in glass bottles has been examined previously as well. 11 The results demonstrate that the cabazitaxel maintains its stability from a physical and chemical point of view for up to 2 weeks after the concentrate-solvent mixture prepared and/or infusion solution is prepared for all storage conditions.…”

“…8–11 A thorough degradation study with another cabazitaxel taxane derivate DS80100717 has also been conducted. 12 The stability in the form of concentration measurement for infusion solution stored in glass bottles has been examined previously as well. 11…”