A rapid and sensitive liquid chromatography-tandem mass spectrometry method（LC-MS/MS）was developed and validated for the quantification of fexofenadine in human plasma,to conduct comparative bioavailability studies....A rapid and sensitive liquid chromatography-tandem mass spectrometry method（LC-MS/MS）was developed and validated for the quantification of fexofenadine in human plasma,to conduct comparative bioavailability studies.Human plasma was extracted with a mixture of dichloromethane-diethyl ether（volume ratio 2∶3）in a basic environment and the extract was separated on a C18 column with a mobile phase consisting of acetonitrile-methanol-10 mmol/L ammonium acetate（volume ratio 45∶45∶10）.The analytes were detected via electrospray ionization（ESI）tandem mass spectrometry in the multiple-reaction-monitoring（MRM）mode.The linearity was within a range of 1-1000 ng/mL.The intra-and inter-day precision were〈4.1% and〈4.8%,respectively,and the accuracy was in the range of 95.0%-105%.The method was applied to the quantification of fexofenadine human plasma from 20 healthy male Chinese volunteers,according to a single dose,randomized,two-way crossover design with a two-week washout period.The mean values of major pharmacokinetic parameters of ρmax,AUC0-48,AUC0-∞,tmax,and t1/2 were determined from the plasma concentration.The analysis of variance（ANOVA）did not show any significant difference between the two products of fexofenadine and 90% confidence intervals fell within the acceptable range for bioequivalence.展开更多
Novel poly（lactide-co-glycolide acid）（PLGA） microspheres were developed for sustained delivery of antisense oligonucleotide（ASO）. First, a new cationic agent, polyethylenimine（PEI） conjugated to linoleic acid...Novel poly（lactide-co-glycolide acid）（PLGA） microspheres were developed for sustained delivery of antisense oligonucleotide（ASO）. First, a new cationic agent, polyethylenimine（PEI） conjugated to linoleic acid（LA）（PEI-LA） was synthesized by reacting PEI（Mw=800） with linoleoyl chloride. Then, PEI-LA was combined with LOR-2501 to form electrostatic complexes at moderate nitrogen-to-phosphate（N/P） molar ratios which were then encapsulated into poly（lactide-co-glycolide） microspheres by a multiple emulsion-solvent evaporation technique. With an increase in ASO/PEI-LA concentration from 5% to 10%, encapsulation efficiency of ASO in the micro- spheres reduced from 72.14% to 57.62%, and the particle size ofmicrospheres increased from 28.58 μm to 34.76 μm. In vitro studies show that the release profile of ASO from microspheres prepared at 7.5% ASO-PEI-LA lasted for 14 d The novel microspheres have a potential use as a sustained release vehicle for ASO.展开更多
文摘A rapid and sensitive liquid chromatography-tandem mass spectrometry method（LC-MS/MS）was developed and validated for the quantification of fexofenadine in human plasma,to conduct comparative bioavailability studies.Human plasma was extracted with a mixture of dichloromethane-diethyl ether（volume ratio 2∶3）in a basic environment and the extract was separated on a C18 column with a mobile phase consisting of acetonitrile-methanol-10 mmol/L ammonium acetate（volume ratio 45∶45∶10）.The analytes were detected via electrospray ionization（ESI）tandem mass spectrometry in the multiple-reaction-monitoring（MRM）mode.The linearity was within a range of 1-1000 ng/mL.The intra-and inter-day precision were〈4.1% and〈4.8%,respectively,and the accuracy was in the range of 95.0%-105%.The method was applied to the quantification of fexofenadine human plasma from 20 healthy male Chinese volunteers,according to a single dose,randomized,two-way crossover design with a two-week washout period.The mean values of major pharmacokinetic parameters of ρmax,AUC0-48,AUC0-∞,tmax,and t1/2 were determined from the plasma concentration.The analysis of variance（ANOVA）did not show any significant difference between the two products of fexofenadine and 90% confidence intervals fell within the acceptable range for bioequivalence.
基金Supported by the National Natural Science Foundation of China（Nos.30870251, 31070309）.
文摘Novel poly（lactide-co-glycolide acid）（PLGA） microspheres were developed for sustained delivery of antisense oligonucleotide（ASO）. First, a new cationic agent, polyethylenimine（PEI） conjugated to linoleic acid（LA）（PEI-LA） was synthesized by reacting PEI（Mw=800） with linoleoyl chloride. Then, PEI-LA was combined with LOR-2501 to form electrostatic complexes at moderate nitrogen-to-phosphate（N/P） molar ratios which were then encapsulated into poly（lactide-co-glycolide） microspheres by a multiple emulsion-solvent evaporation technique. With an increase in ASO/PEI-LA concentration from 5% to 10%, encapsulation efficiency of ASO in the micro- spheres reduced from 72.14% to 57.62%, and the particle size ofmicrospheres increased from 28.58 μm to 34.76 μm. In vitro studies show that the release profile of ASO from microspheres prepared at 7.5% ASO-PEI-LA lasted for 14 d The novel microspheres have a potential use as a sustained release vehicle for ASO.
