Identification of forced degradation products of tedizolid phosphate by liquid chromatography/electrospray ionization tandem mass spectrometry.

In this study, stress degradation behavior of tedizolid phosphate was investigated and structural characterization of its degradation products were performed with the use of the UPLC-MSn and LC-HRMS. The toxicity prediction of the degradation products was performed with web-based prediction system. Tedizolid phosphate was subjected to forced degradation under hydrolytic (acid, base and neutral), oxidative, photolytic and thermal conditions in accordance with ICH guidelines Q1A(R2). The drug was degraded significantly under acid, base and oxidative conditions, while it was relatively stable to neutral, thermal and photolytic conditions. A total of four degradation products were formed. All of them have been identified and characterized based on QTRAP MSn and accurate mass measurements. To the best of our knowledge, three of these impurities were identified for the first time and two of them further synthesized and characterized by NMR spectroscopy.

Pharmacokinetics, bioavailability, metabolism and excretion of δ-viniferin in rats.

A highly rapid and sensitive liquid chromatographic-electrospray ionization tandem mass spectrometric (LC-ESI-MS/MS) method was developed and validated for the determination of trans-δ-viniferin (Rs-1) in rat plasma, urine and feces. All biological samples were prepared by liquid-liquid extraction and hesperetin was included as an internal standard (IS). Chromatographic separation was achieved on a shim-pack XR-ODS column using a gradient mobile phase. MS/MS detection was performed by negative ion electrospray ionization. The method was sensitive with a lower limit of quantification of 1.42 ng/mL and linear over the range of 1.42-2172 ng/mL in all matrices. The method was applied to study the pharmacokinetics, bioavailability, metabolism, and excretion of Rs-1 in rats following a single oral or intravenous dose. Two metabolites, Rs-1 glucuronide and Rs-1 sulfate, were detected in plasma and in urine after administration of Rs-1. The absolute oral bioavailability of Rs-1 was 2.3%, and the total absorption rose to 31.5% with addition of its glucuronide and sulfate metabolites. Only 0.09% of the gavaged dose, including Rs-1 and metabolites, was excreted in the urine, while 60.3% was found in the feces in unchanged form. The results indicate that both poor absorption and extensive metabolism were the important factors that led to the poor bioavailability of Rs-1, which can provide a basis for further studies on structural modification and dosage form design.