Stability-Indicating Determination of Tedizolid Phosphate in the Presence of its Active Form and Possible Degradants.

ABSTRACT

Tedizolid phosphate is an antibiotic prodrug that is metabolized into tedizolid which is used against various resistant bacterial strains. In this study, tedizolid phosphate was subjected to stress degradation conditions, namely, hydrolysis (neutral, acidic and alkaline), thermal, oxidative and photolytic ones. The prodrug was stable toward thermal and photolytic stress conditions, while it showed significant degradation upon applying oxidative and hydrolytic conditions. Two suggested chromatographic methods are described for separation and determination of tedizolid phosphate from the resulted degradation products. The first method is HPLC using Waters Xselect HSS C18 (250 × 4.6 mm, 5 µm) analytical column and mobile phase composed of phosphate buffer (50 mM, pH 6.5)acetonitrile (7030, %v/v) pumped at flow rate of 1.0 mL/min with UV-detection at 300 nm. The second method is a TLC coupled with densitometric quantitation, precoated silica TLC-plates as a stationary phase and a mobile phase of methanolbutanolethyl acetateammonia (33%, w/v) (60202010,%v/v) were used. The chromatographed plates were scanned at 300 nm. The linearity was confirmed over concentration range of 1-100 µg/mL and 1-12 µg/band for HPLC and TLC-densitometric methods, respectively. Both methods were found to be suitable for determination of tedizolid phosphate in pure form and in its pharmaceutical formulations.