The chiral nature of biological systems enables their stereoselective interaction with chiral compounds. It has been well documented that the enantiomers ofa chiral drug may show differences in drug disposition especi...The chiral nature of biological systems enables their stereoselective interaction with chiral compounds. It has been well documented that the enantiomers ofa chiral drug may show differences in drug disposition especially in metabolic behavior. As a result, it is of vital importance to separate the enantiomers of a chiral drug in metabolic studies. This paper discusses enantioselective methods （include high-performance liquid chromatography, gas chromatography, capillary electrophoresis and high-performance liquid chromatography-mass spectrometry） that applied in chiral drug metabolism, using most recent examples where possible.展开更多
Current trends in chiral analysis of pharmaceutical drugs are focused on faster separations and higher separation efficiencies, Core-shell or superficially porous particles （SPP） based chiral stationary phases （CSP...Current trends in chiral analysis of pharmaceutical drugs are focused on faster separations and higher separation efficiencies, Core-shell or superficially porous particles （SPP） based chiral stationary phases （CSPs） provide reduced analysis times while maintaining high column efficiencies and sensitivity. In this study, mobile phase conditions suitable for chiral analyses with electrospray ionization LC-MS were systematically investigated using vancomycin as a representative CSP. The performance of a 2.7 μm SPP based vancomycin CSP （SPP-V） 10 cm ×0.21 cm column was compared to that of a corresponding 5 μm fully porous particles based analogue column. The results demonstrated that the SPP-V column provides higher efficiencies, 2-5 time greater sensitivity and shorter analysis time for a set of 22 basic pharma- ceutical drugs. The SPP-V was successfully applied for the analysis of the degradation products of racemic citalopram whose enantiomers could be selectively identified by MS.展开更多
In the present paper, chiral mesoporous silica nano-cocoon(A-CMSN) functionalized with amino group was synthesized, and its loading and release of indomethacin(IMC), a poorly soluble drug, was studied. Due to the use ...In the present paper, chiral mesoporous silica nano-cocoon(A-CMSN) functionalized with amino group was synthesized, and its loading and release of indomethacin(IMC), a poorly soluble drug, was studied. Due to the use of chiral anionic surfactants as a template, ACMSN possessed 2D hexagonal nano-cocoon morphology with curled channels on its surface, which was quite different from another 2D hexagonal mesoporous silica nanoparticles(MCM-41) with straightway channels. After being loaded into the two silica carriers by hydrogen bond, crystalline IMC converted to amorphous form, leading to the improved drug dissolution. And IMC loading capacity of A-CMSN was higher than MCM-41 because curled loading process originating from curvature chiral channels can hold more drug molecules. Compared with IMC, IMC loaded A-CMSN presented obviously fast release throughout the in vitro release experiment, while IMC loaded MCM-41 released faster than IMC at the initial 5 h then showed controlled slow release afterwards, which was closely related to the mesoporous silica nanoparticles and different channel mesostructures of these two carriers. A-CMSN possessed nano-cocoon morphology with curled 2D hexagonal channel and its channel length was shorter than MCM-41, therefore IMC molecules can easily get rid of the constraint of A-CMSN then to be surrounded by dissolution medium.展开更多
Many therapeutic drugs are racemates;i.e. they are chiral molecules consisting of “left”- and “right-handed” enantiomers (stereoisomers that are mirror images of each other, and are non-superimposable). In some ca...Many therapeutic drugs are racemates;i.e. they are chiral molecules consisting of “left”- and “right-handed” enantiomers (stereoisomers that are mirror images of each other, and are non-superimposable). In some cases, both enantiomers of the drug contribute to some extent (or equally) to the therapeutic effect;in other cases they contribute not at all. The same is true for the adverse effects of racemate drugs: the adverse effects of a racemate drug can be greater-than, less-than, or equal to one or the other enantiomer. An unusual situation arises when a drug consists of “atropisomers”, stereoisomers arising because of hindered rotation about a single chemical bond. We summarize the concept of atropisomerism, and give examples.展开更多
基金National Natural Science Foundation of China(Grant No.30225047 and 30701038)
文摘The chiral nature of biological systems enables their stereoselective interaction with chiral compounds. It has been well documented that the enantiomers ofa chiral drug may show differences in drug disposition especially in metabolic behavior. As a result, it is of vital importance to separate the enantiomers of a chiral drug in metabolic studies. This paper discusses enantioselective methods （include high-performance liquid chromatography, gas chromatography, capillary electrophoresis and high-performance liquid chromatography-mass spectrometry） that applied in chiral drug metabolism, using most recent examples where possible.
基金supported by the Robert A.Welch Foundation(Y0026)the French National Center for Scientific Research(ISA-CNRS-UMR5280)
文摘Current trends in chiral analysis of pharmaceutical drugs are focused on faster separations and higher separation efficiencies, Core-shell or superficially porous particles （SPP） based chiral stationary phases （CSPs） provide reduced analysis times while maintaining high column efficiencies and sensitivity. In this study, mobile phase conditions suitable for chiral analyses with electrospray ionization LC-MS were systematically investigated using vancomycin as a representative CSP. The performance of a 2.7 μm SPP based vancomycin CSP （SPP-V） 10 cm ×0.21 cm column was compared to that of a corresponding 5 μm fully porous particles based analogue column. The results demonstrated that the SPP-V column provides higher efficiencies, 2-5 time greater sensitivity and shorter analysis time for a set of 22 basic pharma- ceutical drugs. The SPP-V was successfully applied for the analysis of the degradation products of racemic citalopram whose enantiomers could be selectively identified by MS.
基金supported by Postdoctoral Science Foundation of China 2017M611268
文摘In the present paper, chiral mesoporous silica nano-cocoon(A-CMSN) functionalized with amino group was synthesized, and its loading and release of indomethacin(IMC), a poorly soluble drug, was studied. Due to the use of chiral anionic surfactants as a template, ACMSN possessed 2D hexagonal nano-cocoon morphology with curled channels on its surface, which was quite different from another 2D hexagonal mesoporous silica nanoparticles(MCM-41) with straightway channels. After being loaded into the two silica carriers by hydrogen bond, crystalline IMC converted to amorphous form, leading to the improved drug dissolution. And IMC loading capacity of A-CMSN was higher than MCM-41 because curled loading process originating from curvature chiral channels can hold more drug molecules. Compared with IMC, IMC loaded A-CMSN presented obviously fast release throughout the in vitro release experiment, while IMC loaded MCM-41 released faster than IMC at the initial 5 h then showed controlled slow release afterwards, which was closely related to the mesoporous silica nanoparticles and different channel mesostructures of these two carriers. A-CMSN possessed nano-cocoon morphology with curled 2D hexagonal channel and its channel length was shorter than MCM-41, therefore IMC molecules can easily get rid of the constraint of A-CMSN then to be surrounded by dissolution medium.
文摘Many therapeutic drugs are racemates;i.e. they are chiral molecules consisting of “left”- and “right-handed” enantiomers (stereoisomers that are mirror images of each other, and are non-superimposable). In some cases, both enantiomers of the drug contribute to some extent (or equally) to the therapeutic effect;in other cases they contribute not at all. The same is true for the adverse effects of racemate drugs: the adverse effects of a racemate drug can be greater-than, less-than, or equal to one or the other enantiomer. An unusual situation arises when a drug consists of “atropisomers”, stereoisomers arising because of hindered rotation about a single chemical bond. We summarize the concept of atropisomerism, and give examples.
