Ribociclib is a highly specific CDK4/6 inhibitor. Determination of the metabolism of ribociclib is required during the drug development stage. In this study, metabolic profiles of ribociclib were investigated using rat and human liver microsomes. Metabolites were structurally identified by liquid chromatography electrospray ionization high‐resolution mass spectrometry operated in positive‐ion mode. The metabolites were characterized by accurate masses, MS2 spectra and retention times. With rat and human liver microsomes, a total of 10 metabolites were detected and further identified. No human‐specific metabolites were detected. The metabolic pathways of ribociclib were oxygenation, demethylation and dealkylation. Most importantly, two glutathione (GSH) adducts were identified in human liver microsomes fortified with GSH. The formation of the GSH adducts was hypothesized to be through the oxidation of electron‐rich 1,4‐benzenediamine to a 1,4‐diiminoquinone intermediate, which is highly reactive and can be trapped by GSH to form stable metabolites. The current study provides an overview of the metabolic profiles of ribociclib in vitro, which will be of great help in understanding the efficacy and toxicity of this drug.

In this paper, a high-order cylindrical beam model, where the shear deformation is taken into account, will be used to analyze the buckling behaviors of the functionally graded cylindrical beams with radially and axially varying material inhomogeneities. The coupled governing equations for buckling of a cylindrical beam under axial compression are derived, which can be translated into a single differential equation by introducing an auxiliary function. The shifted Chebyshev polynomials are used to compute the critical buckling loads for kinds of boundary conditions. By comparing with the three-dimensional solutions for buckling of homogeneous circular beams, the validity of the introduced model is confirmed. Two typical material property distributions defined by the exponential- and power-law are considered. A parametric study is carried out to investigate the effects of material gradient indexes on the critical buckling loads.