Zwitterionic sulfobetaine-based monolithic stationary phases have attracted increasing attention for their use in hydrophilic interaction chromatography.In this study,a novel hydrophilic polymeric monolith was fabrica...Zwitterionic sulfobetaine-based monolithic stationary phases have attracted increasing attention for their use in hydrophilic interaction chromatography.In this study,a novel hydrophilic polymeric monolith was fabricated through photo-initiated copolymerization of 3-(3-vinyl-1-imidazolio)-1-propanesulfonate(SBVI)with pentaerythritol triacrylate using methanol and tetrahydrofuran as the porogenic system.Notably,the duration for the preparation of this novel monolith was as little as 5 min,which was significantly shorter than that required for previously reported sulfobetaine-based monoliths prepared via conventional thermally initiated copolymerization.Moreover,these monoliths showed good morphology,permeability,porosity(62.4%),mechanical strength(over 15 MPa),column efficiency(51,230 plates/m),and reproducibility(relative standard deviations for all analytes were lower than 4.6%).Mechanistic studies indicated that strong hydrophilic and negative electrostatic interactions might be responsible for the retention of polar analytes on the zwitterionic SBVI-based monolith.In particular,the resulting monolith exhibited good anti-protein adhesion ability and low nonspecific protein adsorption.These excellent features seem to favor its application in bioanalysis.Therefore,the novel zwitterionic sulfobetaine-based monolith was successfully employed for the highly selective separation of small bioactive compounds and the efficient enrichment of N-glycopeptides from complex samples.In this study,we prepared a novel zwitterionic sulfobetaine-based monolith with good performance and developed a simpler and faster method for preparation of zwitterionic monoliths.展开更多
Porous graphene(PG) has potential applications in numerous fields because of the existence of nanopores in the plane. In this study, porous graphene decorated silica microspheres(Sil-PG) were successfully fabricated b...Porous graphene(PG) has potential applications in numerous fields because of the existence of nanopores in the plane. In this study, porous graphene decorated silica microspheres(Sil-PG) were successfully fabricated by assembling PG onto the silica particles surface in deep eutectic solvents(DESs).Experimental results demonstrate that this new stationary phase can facilitate the separation of six sulfonamides compounds in hydrophilic chromatographic conditions. The successful synthesis of the SilPG stationary phase provides a basis for the application of porous graphene-modified materials as the stationary phase for liquid chromatography, and offers the possibility to broaden the application of PG in the field of chromatography.展开更多
A one-step procedure to hydrophilize monodisperse poly（chloromethyl-styrene-co-divinylbenzene） beads has been presented with 2-hydroxy-3-[4-（hydroxymethyl）-1H-1,2,3-triazol-1-yl]propy1 2-methylacrylate（HTMA） as ...A one-step procedure to hydrophilize monodisperse poly（chloromethyl-styrene-co-divinylbenzene） beads has been presented with 2-hydroxy-3-[4-（hydroxymethyl）-1H-1,2,3-triazol-1-yl]propy1 2-methylacrylate（HTMA） as monomer by surface-initiated atom transfer radical polymerization（SI-ATRP）.The length of the grafted poly（HTMA） chain was varied via controlling the ratio of HTMA to initiator on the surface of the beads.Using these grafted beads as the stationary phase in hydrophilic interaction chromatography,good separation was obtained for nucleosides in the mobile phase of acetonitrile-water.It was also found that the retention time and selectivity of solutes showed a positive relationship with the length of the grafted poly（HTMA） chain.展开更多
A reversed phase (RP)/hydrophilic interaction (HILIC)/ion exchange (IEX) mixed tri-mode stationary phase (TMSP) has been prepared via a divergent synthesis scheme starting from propylamine on silica then by amine-epox...A reversed phase (RP)/hydrophilic interaction (HILIC)/ion exchange (IEX) mixed tri-mode stationary phase (TMSP) has been prepared via a divergent synthesis scheme starting from propylamine on silica then by amine-epoxy reactions with 1,4-butanedioldiglycidyl ether and tertiary amines (N,Ndimethyldecylamine, DMDA). Its retention mechanism was found to follow RP/HILIC/IEX mixed-mode.The stop-flow test revealed that TMSP had good compatibility with 100% aqueous mobile phase. It demonstrated effective separation towards several kinds of compounds or drug molecules and their counterions within a single run.展开更多
RNA modification has recently been proposed to play important roles in biological regulation. The detection and quantification of RNA modifications generally are challenging tasks since most of the modifications exist...RNA modification has recently been proposed to play important roles in biological regulation. The detection and quantification of RNA modifications generally are challenging tasks since most of the modifications exist in low abundance in vivo. Here we developed an on-line trapping/capillary hydrophilic-interaction liquid chromatography/electrospray ionization-mass spectrometry(on-line trapping/cHILIC/MS) method for sensitive and simultaneous quantification of RNA modifications of N^6-methyladenosine(m^6A) and 5-methylcytosine(5-mC) from human blood. The hydrophilic organic-silica hybrid monolith was prepared using sol-gel combined with "thiol-ene" click reaction for the separation of nucleosides. A poly(MAA-co-EGDMA) monolithic capillary was used as the on-line trapping column.With the developed on-line trapping/cHILIC/MS analytical platform, the detection limits of m^6A and 5-mC can reach to 0.06 fmol and 0.10 fmol. We then investigated the contents of m^6A and 5-mC in human blood RNA from healthy persons at the age of 6-14 and 60-68 years. Our results showed that both m^6A and 5-mC contents were significantly decreased in elder persons, suggesting the RNA modifications of m^6A and 5-mC are correlated to aging.展开更多
Aryloxypropanolamine is an essential structural scaffold for a variety of b-adrenergic receptor antagonists such as metoprolol.Molecules with such a structural motif tend to degrade into α,β ehydroxypropanolamine im...Aryloxypropanolamine is an essential structural scaffold for a variety of b-adrenergic receptor antagonists such as metoprolol.Molecules with such a structural motif tend to degrade into α,β ehydroxypropanolamine impurities via a radicaleinitiated oxidation pathway.These impurities are typically polar and nonchromophoric,and are thus often overlooked using traditional reversed phase chromatography and UV detection.In this work,stress testing of metoprolol confirmed the generation of 3-isopropylamino-1,2-propanediol as a degradation product,which is a specified impurity of metoprolol in the European Pharmacopoeia(impurity N).To ensure the safety and quality of metoprolol drug products,hydrophilic interaction chromatography(HILIC)methods using Halo Penta HILIC column(150mm×4.6 mm,5 μm)coupled with charged aerosol detection(CAD)were developed and optimized for the separation and quantitation of metoprolol impurity N in metoprolol drug products including metoprolol tartrate injection,metoprolol tartrate tablets,and metoprolol succinate extended-release tablets.These HILIC-CAD methods were validated per USP validation guidelines with respect to specificity,linearity,accuracy,and precision,and have been successfully applied to determine impurity N in metoprolol drug products.展开更多
Hydrophilic metabolites play important roles in cellular energy metabolism,signal transduction,immunity.However,there are challenges in both identification and quantification of the hydrophilic metabolites due to thei...Hydrophilic metabolites play important roles in cellular energy metabolism,signal transduction,immunity.However,there are challenges in both identification and quantification of the hydrophilic metabolites due to their weak interactions with C18-reversed-phase liquid chromatography(RPLC),leading to poor retention of hydrophilic metabolites on the columns.Many strategies have been put forward to increase the retention behavior of hydrophilic metabolites in the RPLC system.Non-derivatization methods are mainly focused on the development of new chromatographic techniques with different separation mechanisms,such as capillary electrophoresis,ion-pairing RPLC etc.Derivatization methods improve the hydrophobicity of metabolites and can enhance the MS response.This review mainly focused on the illustration of challenges of LCMS in the analysis of hydrophilic metabolomics field,and summarized the non-derivatization and derivatization strategies,with the intention of providing multiple choices for analysis of hydrophilic metabolites.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.:82173773 and 82073806)the Natural Science Foundation of Guangdong Province,China(Grant Nos.:2020A1515010569 and 2021A0505030039)Science and Technology Program of Guangzhou,China(Grant No.:202102020729).
文摘Zwitterionic sulfobetaine-based monolithic stationary phases have attracted increasing attention for their use in hydrophilic interaction chromatography.In this study,a novel hydrophilic polymeric monolith was fabricated through photo-initiated copolymerization of 3-(3-vinyl-1-imidazolio)-1-propanesulfonate(SBVI)with pentaerythritol triacrylate using methanol and tetrahydrofuran as the porogenic system.Notably,the duration for the preparation of this novel monolith was as little as 5 min,which was significantly shorter than that required for previously reported sulfobetaine-based monoliths prepared via conventional thermally initiated copolymerization.Moreover,these monoliths showed good morphology,permeability,porosity(62.4%),mechanical strength(over 15 MPa),column efficiency(51,230 plates/m),and reproducibility(relative standard deviations for all analytes were lower than 4.6%).Mechanistic studies indicated that strong hydrophilic and negative electrostatic interactions might be responsible for the retention of polar analytes on the zwitterionic SBVI-based monolith.In particular,the resulting monolith exhibited good anti-protein adhesion ability and low nonspecific protein adsorption.These excellent features seem to favor its application in bioanalysis.Therefore,the novel zwitterionic sulfobetaine-based monolith was successfully employed for the highly selective separation of small bioactive compounds and the efficient enrichment of N-glycopeptides from complex samples.In this study,we prepared a novel zwitterionic sulfobetaine-based monolith with good performance and developed a simpler and faster method for preparation of zwitterionic monoliths.
基金Financial supports from the National Natural Science Foundation of China (Nos. 21822407 and 21675164)the funds for Distinguished Young Scientists of Gansu (No. 1506RJDA281) are gratefully acknowledged
文摘Porous graphene(PG) has potential applications in numerous fields because of the existence of nanopores in the plane. In this study, porous graphene decorated silica microspheres(Sil-PG) were successfully fabricated by assembling PG onto the silica particles surface in deep eutectic solvents(DESs).Experimental results demonstrate that this new stationary phase can facilitate the separation of six sulfonamides compounds in hydrophilic chromatographic conditions. The successful synthesis of the SilPG stationary phase provides a basis for the application of porous graphene-modified materials as the stationary phase for liquid chromatography, and offers the possibility to broaden the application of PG in the field of chromatography.
基金supported by National Natural Science Foundation of China(No.20975080)Program for New Century Excellent Talents in University(No.NCET-08-0892)+1 种基金Major State Basic Research Development Program of China(No.2009CB26608)Natural Science Foundation of Ningxia Province(No.NZ0914)
文摘A one-step procedure to hydrophilize monodisperse poly（chloromethyl-styrene-co-divinylbenzene） beads has been presented with 2-hydroxy-3-[4-（hydroxymethyl）-1H-1,2,3-triazol-1-yl]propy1 2-methylacrylate（HTMA） as monomer by surface-initiated atom transfer radical polymerization（SI-ATRP）.The length of the grafted poly（HTMA） chain was varied via controlling the ratio of HTMA to initiator on the surface of the beads.Using these grafted beads as the stationary phase in hydrophilic interaction chromatography,good separation was obtained for nucleosides in the mobile phase of acetonitrile-water.It was also found that the retention time and selectivity of solutes showed a positive relationship with the length of the grafted poly（HTMA） chain.
基金financially supported by the National Natural Science Foundation of China(Nos. 21477037, 21322502)the Outstanding Young Talent Cultivation Fund of East China University of Science and Technology
文摘A reversed phase (RP)/hydrophilic interaction (HILIC)/ion exchange (IEX) mixed tri-mode stationary phase (TMSP) has been prepared via a divergent synthesis scheme starting from propylamine on silica then by amine-epoxy reactions with 1,4-butanedioldiglycidyl ether and tertiary amines (N,Ndimethyldecylamine, DMDA). Its retention mechanism was found to follow RP/HILIC/IEX mixed-mode.The stop-flow test revealed that TMSP had good compatibility with 100% aqueous mobile phase. It demonstrated effective separation towards several kinds of compounds or drug molecules and their counterions within a single run.
基金financially supported by the National Natural Science Foundation of China (Nos. 21522507, 21672166, 21728802, 21721005)
文摘RNA modification has recently been proposed to play important roles in biological regulation. The detection and quantification of RNA modifications generally are challenging tasks since most of the modifications exist in low abundance in vivo. Here we developed an on-line trapping/capillary hydrophilic-interaction liquid chromatography/electrospray ionization-mass spectrometry(on-line trapping/cHILIC/MS) method for sensitive and simultaneous quantification of RNA modifications of N^6-methyladenosine(m^6A) and 5-methylcytosine(5-mC) from human blood. The hydrophilic organic-silica hybrid monolith was prepared using sol-gel combined with "thiol-ene" click reaction for the separation of nucleosides. A poly(MAA-co-EGDMA) monolithic capillary was used as the on-line trapping column.With the developed on-line trapping/cHILIC/MS analytical platform, the detection limits of m^6A and 5-mC can reach to 0.06 fmol and 0.10 fmol. We then investigated the contents of m^6A and 5-mC in human blood RNA from healthy persons at the age of 6-14 and 60-68 years. Our results showed that both m^6A and 5-mC contents were significantly decreased in elder persons, suggesting the RNA modifications of m^6A and 5-mC are correlated to aging.
文摘Aryloxypropanolamine is an essential structural scaffold for a variety of b-adrenergic receptor antagonists such as metoprolol.Molecules with such a structural motif tend to degrade into α,β ehydroxypropanolamine impurities via a radicaleinitiated oxidation pathway.These impurities are typically polar and nonchromophoric,and are thus often overlooked using traditional reversed phase chromatography and UV detection.In this work,stress testing of metoprolol confirmed the generation of 3-isopropylamino-1,2-propanediol as a degradation product,which is a specified impurity of metoprolol in the European Pharmacopoeia(impurity N).To ensure the safety and quality of metoprolol drug products,hydrophilic interaction chromatography(HILIC)methods using Halo Penta HILIC column(150mm×4.6 mm,5 μm)coupled with charged aerosol detection(CAD)were developed and optimized for the separation and quantitation of metoprolol impurity N in metoprolol drug products including metoprolol tartrate injection,metoprolol tartrate tablets,and metoprolol succinate extended-release tablets.These HILIC-CAD methods were validated per USP validation guidelines with respect to specificity,linearity,accuracy,and precision,and have been successfully applied to determine impurity N in metoprolol drug products.
基金This work was supported by grant from the National Key R&D Program of China(2017YFC0906800).
文摘Hydrophilic metabolites play important roles in cellular energy metabolism,signal transduction,immunity.However,there are challenges in both identification and quantification of the hydrophilic metabolites due to their weak interactions with C18-reversed-phase liquid chromatography(RPLC),leading to poor retention of hydrophilic metabolites on the columns.Many strategies have been put forward to increase the retention behavior of hydrophilic metabolites in the RPLC system.Non-derivatization methods are mainly focused on the development of new chromatographic techniques with different separation mechanisms,such as capillary electrophoresis,ion-pairing RPLC etc.Derivatization methods improve the hydrophobicity of metabolites and can enhance the MS response.This review mainly focused on the illustration of challenges of LCMS in the analysis of hydrophilic metabolomics field,and summarized the non-derivatization and derivatization strategies,with the intention of providing multiple choices for analysis of hydrophilic metabolites.
