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

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 (70:30, %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 methanol:butanol:ethyl acetate:ammonia (33%, w/v) (60:20:20:10,%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.

Eco-Friendly Chromatographic Methods for Determination of Acemetacin and Indomethacin; Greenness Profile Assessment.

BACKGROUND: The green chemistry approach was developed for the purpose of saving the environment by using green solvents. Applying green analytical chemistry principles to traditional methods is considered a challenge. Acemetacin is a commonly used analgesic prodrug that bioactivates to indomethacin. OBJECTIVE: Developing two simple, eco-friendly chromatographic methods for simultaneous determination of acemetacin and indomethacin. METHOD: The first method is HPLC-DAD. Separation was performed on a Waters XBridge® Shield RP18 (250 × 4.6 mm, 5 µm) analytical column with ethanol-ammonium acetate buffer (50 mM, pH 3.5 ± 0.1; 60:40, v/v) as a mobile phase at a flow rate of 1 mL/min at 25 ± 0.5°C and UV detection at 254 nm. The other method is TLC coupled with densitometric quantification using pre-coated silica TLC plates and butanol-ethyl acetate (70:30, v/v) elution system. The plates were scanned at 254 nm. RESULTS: Both methods were validated according to International Conference on Harmonization guidelines. Linearity was confirmed for both over a concentration range of 1-100 µg/mL for the HPLC method and 0.2-7 µg/band for TLC-densitometric method. The methods' greenness was evaluated by the National Environmental Methods Index, Eco-Scale, Green Analytical Procedure Index metrics and Analytical GREEnness Metric Approach. CONCLUSIONS: The proposed methods were found to be suitable for determination of studied drugs in their marketed formulations and is suggested for routine analysis in quality control laboratories. HIGHLIGHTS: The developed HPLC method shortened the elution time of the analyzed drugs saving more time and money and the TLC method lowered the drugs' detection limit. HPLC and TLC methods were validated for the assay of acemetacin and indomethacin. The methods' greenness was evaluated and compared to published methods. The developed HPLC method shortened the elution time of the analyzed drugs, saving time and money and the TLC method lowered the drugs' detection limit.