The solution and solid-state degradation study followed by identification of tedizolid related compounds in medicinal product by high performance liquid chromatography with diode array and tandem mass spectrometry detection

Abstract

The aim of the study was to investigate the intrinsic stability and to identify potential degradation products of tedizolid disodium phosphate (TED-OPO₃Na₂), which belongs to the antimicrobial agents of the oxazolidinone class. Tedizolid, as disodium phosphate (prodrug), is registered under the trade name SIVEXTRO®, at a dose of 200 mg, in the form of powder for injection or infusion. The stability-indicating assay method was optimised using HPLC with diode array detection and with electrospray ionisation time-of-flight mass spectrometry. In solution-state studies, the forced decomposition of TED-OPO₃Na₂ carried out under acidic, basic, oxidative, photocatalytic, and thermal conditions revealed the lability of TED-OPO₃Na₂ to acidic, basic, and photocatalytic (UV) conditions, while it was relatively stable in oxidative conditions and during thermolysis processes. The kinetics of degradation and shelf-life values in solution-state studies were determined, and activation energies were calculated for alkaline and thermolytic degradation. In contrast, in the solid state degradation study, TED-OPO₃Na₂ was stable under thermal conditions at high humidity and in visible light, while moderate degradation was observed under thermal conditions of low humidity and ultraviolet light. The developed method enabled the identification of 12 new degradation products and 3 new by-products.

Keywords: Mass spectrometry; Oxazolidinone; Reaction kinetics; Stability-indicating; Tedizolid.