Two polysaccharide-based chiral stationary phase columns were evaluated to improve the previous partial chiral peak separation to a baseline-resolved separation of the INGREZZA® drug substance and its diastereome...Two polysaccharide-based chiral stationary phase columns were evaluated to improve the previous partial chiral peak separation to a baseline-resolved separation of the INGREZZA® drug substance and its diastereomers. Moreover, the tailing factor (Tf) variation was studied to investigate chiral column degradation and regeneration and to optimize chiral column performance and efficiency.展开更多
Molecularly imprinted polymers （MIPs）, using （S）-naproxen as template and the combination of butyl methacrylate （BMA） and MAA （1：1 molar ratio） as functional monomers were synthesized by an in situ polymeriza...Molecularly imprinted polymers （MIPs）, using （S）-naproxen as template and the combination of butyl methacrylate （BMA） and MAA （1：1 molar ratio） as functional monomers were synthesized by an in situ polymerization reaction. The rendered monolithic column was evaluated in HPLC mode. The result showed that the monolithic MIPs with the combination of two monomers produced better chiral resolution of rac-naproxen （Rs = 1.55） and column efficiencies of imprinted molecules （N = 2860 plates/m） than that with pure MAA.展开更多
A selective, sensitive and high throughput liquid chromatography-tandem mass spectro-metry （LC-ESI-MS/MS） method has been developed for separation and quantification of metoprolol enantiomers on a chiral Lux Amylose...A selective, sensitive and high throughput liquid chromatography-tandem mass spectro-metry （LC-ESI-MS/MS） method has been developed for separation and quantification of metoprolol enantiomers on a chiral Lux Amylose-2 （250 mm＆#215;4.6 mm, 5 mm） column. Solid phase extraction of （S）-（-）- and （R）-（t）-metoprolol and rac-metoprolol-d6 as an internal standard （IS） was achieved on Lichrosep DVB HL cartridges employing 200 mL human plasma. Both the analytes were chromatographically separated with a resolution factor of 2.24 using 15 mM ammonium acetate in water, pH 5.0 and 0.1% （v/v） diethyl amine in acetonitrile （50：50, v/v） as the mobile phase within 7.0 min. The precursor-product ion transitions for the enantiomers and IS were monitored in the multiple reaction monitoring and positive ionization mode. The method was validated over the concentration range of 0.500-500 ng/mL for both the enantiomers. Matrix effect was assessed by post-column analyte infusion experiment and the mean extraction recovery was greater than 94.0% for both the enantiomers at all quality control levels. The stability of analytes was evaluated in plasma and whole blood under different storage conditions. The method was successfully applied to a clinical study in 14 healthy volunteers after oral administration of 200 mg metoprolol tablet under fasting conditions. The assay reproducibility is shown by reanalysis of 68 incurred samples. The suitability of the developed method was assessed in comparison with＆amp;nbsp;different chromatographic methods developed for stereoselective analysis of metoprolol in biological matrices.展开更多
Egg white protein bonded columns were developed for HPLC. These columns can be used under aqueous mobile phase and separate various kinds of drug enantiomers. Hyphenated techniques using protein bonded columns with LC...Egg white protein bonded columns were developed for HPLC. These columns can be used under aqueous mobile phase and separate various kinds of drug enantiomers. Hyphenated techniques using protein bonded columns with LC/MS and/or column switching have been recognized as integral methods in pharmaceutical research to analyze drug enantiomers. Therefore, these methods are very useful for research fields of pharmacokinetics and pharmacology.展开更多
文摘Two polysaccharide-based chiral stationary phase columns were evaluated to improve the previous partial chiral peak separation to a baseline-resolved separation of the INGREZZA® drug substance and its diastereomers. Moreover, the tailing factor (Tf) variation was studied to investigate chiral column degradation and regeneration and to optimize chiral column performance and efficiency.
基金This work was supported by the National Natural Science Foundation of China(20575045)outstanding scholar programs of Tianjin Medical University(to Z.S.Liu).
文摘Molecularly imprinted polymers （MIPs）, using （S）-naproxen as template and the combination of butyl methacrylate （BMA） and MAA （1：1 molar ratio） as functional monomers were synthesized by an in situ polymerization reaction. The rendered monolithic column was evaluated in HPLC mode. The result showed that the monolithic MIPs with the combination of two monomers produced better chiral resolution of rac-naproxen （Rs = 1.55） and column efficiencies of imprinted molecules （N = 2860 plates/m） than that with pure MAA.
文摘A selective, sensitive and high throughput liquid chromatography-tandem mass spectro-metry （LC-ESI-MS/MS） method has been developed for separation and quantification of metoprolol enantiomers on a chiral Lux Amylose-2 （250 mm＆#215;4.6 mm, 5 mm） column. Solid phase extraction of （S）-（-）- and （R）-（t）-metoprolol and rac-metoprolol-d6 as an internal standard （IS） was achieved on Lichrosep DVB HL cartridges employing 200 mL human plasma. Both the analytes were chromatographically separated with a resolution factor of 2.24 using 15 mM ammonium acetate in water, pH 5.0 and 0.1% （v/v） diethyl amine in acetonitrile （50：50, v/v） as the mobile phase within 7.0 min. The precursor-product ion transitions for the enantiomers and IS were monitored in the multiple reaction monitoring and positive ionization mode. The method was validated over the concentration range of 0.500-500 ng/mL for both the enantiomers. Matrix effect was assessed by post-column analyte infusion experiment and the mean extraction recovery was greater than 94.0% for both the enantiomers at all quality control levels. The stability of analytes was evaluated in plasma and whole blood under different storage conditions. The method was successfully applied to a clinical study in 14 healthy volunteers after oral administration of 200 mg metoprolol tablet under fasting conditions. The assay reproducibility is shown by reanalysis of 68 incurred samples. The suitability of the developed method was assessed in comparison with＆amp;nbsp;different chromatographic methods developed for stereoselective analysis of metoprolol in biological matrices.
文摘Egg white protein bonded columns were developed for HPLC. These columns can be used under aqueous mobile phase and separate various kinds of drug enantiomers. Hyphenated techniques using protein bonded columns with LC/MS and/or column switching have been recognized as integral methods in pharmaceutical research to analyze drug enantiomers. Therefore, these methods are very useful for research fields of pharmacokinetics and pharmacology.
