Discrimination of polysorbate 20 by high-performance liquid chromatography-charged aerosol detection and characterization for components by expanding compound database and library

Analyzing polysorbate 20(PS20)composition and the impact of each component on stability and safety is crucial due to formulation variations and individual tolerance.The similar structures and polarities of PS20 components make accurate separation,identification,and quantification challenging.In this work,a high-resolution quantitative method was developed using single-dimensional high-performance liquid chromatography(HPLC)with charged aerosol detection(CAD)to separate 18 key components with multiple esters.The separated components were characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS)with an identical gradient as the HPLC-CAD analysis.The polysorbate compound database and library were expanded over 7-time compared to the commercial database.The method investigated differences in PS20 samples from various origins and grades for different dosage forms to evaluate the composition-process relationship.UHPLC-Q-TOF-MS identified 1329 to 1511 compounds in 4 batches of PS20 from different sources.The method observed the impact of 4 degradation conditions on peak components,identifying stable components and their tendencies to change.HPLC-CAD and UHPLC-Q-TOF-MS results provided insights into fingerprint differences,distinguishing quasi products.

Construction of enantioenriched eight-membered lactones via Pd-catalyzed asymmetric(6+2)dipolar annulation

Concise synthesis of eight-membered lactones,a kind of medium-sized heterocycles widespread in many bioactive natural products,is highly significant.However,it still remains a challenge due to unfavorable entropic factor and transannular interaction.Herein,we disclose an enantioselective synthesis of eight-membered lactones through a Pd-catalyzed asymmetric(6+2)dipolar annulation of vinyl oxetanes andα-diazo ketones(20 examples,up to 93%yield and 95:5 er).This reaction features simple operation,mild conditions and good enantiocontrol,especially the challenging chiral all-carbon quaternary stereocenter.A newly developed chiral hybrid P,S ligand and the in-situ photo-generation of ketene dipolarophiles are crucial to this success.

Serration Behavior in Zr-Cu-Al Glass-forming Systems

The metallic glass matrix composites（MGMCs）and bulk metallic glasses（BMGs）were studied by statistical analysis during plastic deformation at the strain rates of 2×10^-2,2×10^-3,and 2×10^-4 s^-1,respectively.No serration events occur in both MGMCs and BMGs during compression tests at the strain rate of 2×10^-2 s^-1.When deformed at the strain rate of 2×10^-3 s^-1,the BMG displays a larger plasticity,which is due to the larger serration events followed by a series of small serrations caused by the continuous movement of free volume.The amplitudes and elastic-energy densities increase with increasing the strain rates owing to many serrations in MGMCs.It is deduced that the Young′s modulus decreases from the normalized stress drop and fluctuations are observed on stressstrain curves,which is attributed to a lower coefficient according to the stick-slip model.