We developed a chiral HPLC method for the separation and analysis ofnaftopidil enantiomers. The two enantiomers of naflopidil were separated using a Chiralpak AD-H （250 mm×4.6 mm, 5 μm） column and monitored at...We developed a chiral HPLC method for the separation and analysis ofnaftopidil enantiomers. The two enantiomers of naflopidil were separated using a Chiralpak AD-H （250 mm×4.6 mm, 5 μm） column and monitored at the wavelength of 283 nm. The isocratic mobile phase consisting of hexane-isopropanol-diethylamine （85：15：0.1, v/v/v） was pumped at a flow rate of 1.0 mL/min. Under these chromatographic conditions, R-naflopidil and S-naftopidil were well separated and had good linearity in the ranges of 0.78-50 μg/mL （r = 0.9999） and 0.84-54 μg/mL （r = 0.9998）, respectively. The relative standard deviations （RSD） of intra- and inter-day assays were no more than 0.5% and 0.7%, respectively. This improved method for the separation and quantitative determination of naflopidil enantiomers can be used for the quality control of synthesized naflopidil product.展开更多
Effective enantioseparation of Naftopidil and its derivatives by HPLC was accomplished using several different polysaccharide-based chiral stationary phases（CSPs）.In normal-phase mode,the compounds were eluted on fo...Effective enantioseparation of Naftopidil and its derivatives by HPLC was accomplished using several different polysaccharide-based chiral stationary phases（CSPs）.In normal-phase mode,the compounds were eluted on four coated-and two immobilized-columns with the mixture of n-hexane,isopropanol and diethylamine（DEA）.Polysaccharide tris（3,5- dimethylphenyl carbamate） was shown to be the best enantiomer selector.In addition,the immobilized column packed with Chiralpak IA or IB was applied under polar-organic and reversed-phase conditions,both of which exhibited excellent enantioselectivity for Naftopidil and its derivatives.Furthermore,the underlying possible chiral recognition mechanisms were discussed.展开更多
Chiral drug naftopidil(NAF), a specific α1D-adrenoceptor(AR) antagonist for the treatment of benign prostatic hyperplasia, was used in racemic form for several decades. Our recent work declared that NAF enantiomers s...Chiral drug naftopidil(NAF), a specific α1D-adrenoceptor(AR) antagonist for the treatment of benign prostatic hyperplasia, was used in racemic form for several decades. Our recent work declared that NAF enantiomers showed the same antagonistic effects on the α1D-AR, but the binding mechanism of these two stereochemical NAF isomers to the α1D receptor remained unclear. Herein, we reported the crystallographic structures of optically pure NAF stereoisomers for the first time and unambiguously determined their absolute configurations. The crystal data of R and S enantiomers matched satisfactorily the pharmacophore model for α1D-selective antagonists. Based on the constructed α1D homology model,molecular docking studies shed light on the molecular mechanism of NAF enantiomers binding to α1D-AR. The results indicated that NAF enantiomers exhibited the very similar binding poses and occupied the same binding pocket.展开更多
目的:探讨萘哌地尔(Naftop id il)治疗女性尿道综合征的有效性和安全性。方法:38例患者采用自身对照试验,洗脱期1周,治疗期4周,应用萘哌地尔片25mg,每晚口服。以尿道综合征症状评分(FUSS)为主要疗效指标,以生活质量评分(QOL)为次要观察...目的:探讨萘哌地尔(Naftop id il)治疗女性尿道综合征的有效性和安全性。方法:38例患者采用自身对照试验,洗脱期1周,治疗期4周,应用萘哌地尔片25mg,每晚口服。以尿道综合征症状评分(FUSS)为主要疗效指标,以生活质量评分(QOL)为次要观察指标。结果:治疗2周后患者症状开始好转,4周后疗效显著。治疗前后的FUSS、QOL相比较,差异显示均有统计学意义(P<0.01及P<0.05),总有效率为76.31%。结论:萘哌地尔治疗女性尿道综合征有效、安全。展开更多
基金Guangzhou Science and Technology Projects of Apecial Areas of Innovative Medicines (Grant No.2006Z2-E4011)2006 Guangdong Province Technology Projects (Grant No. 2006B35501003)
文摘We developed a chiral HPLC method for the separation and analysis ofnaftopidil enantiomers. The two enantiomers of naflopidil were separated using a Chiralpak AD-H （250 mm×4.6 mm, 5 μm） column and monitored at the wavelength of 283 nm. The isocratic mobile phase consisting of hexane-isopropanol-diethylamine （85：15：0.1, v/v/v） was pumped at a flow rate of 1.0 mL/min. Under these chromatographic conditions, R-naflopidil and S-naftopidil were well separated and had good linearity in the ranges of 0.78-50 μg/mL （r = 0.9999） and 0.84-54 μg/mL （r = 0.9998）, respectively. The relative standard deviations （RSD） of intra- and inter-day assays were no more than 0.5% and 0.7%, respectively. This improved method for the separation and quantitative determination of naflopidil enantiomers can be used for the quality control of synthesized naflopidil product.
基金Guangzhou mega Projects of Science Research in 2009(Grant No.2009A1-E011-7)
文摘Effective enantioseparation of Naftopidil and its derivatives by HPLC was accomplished using several different polysaccharide-based chiral stationary phases（CSPs）.In normal-phase mode,the compounds were eluted on four coated-and two immobilized-columns with the mixture of n-hexane,isopropanol and diethylamine（DEA）.Polysaccharide tris（3,5- dimethylphenyl carbamate） was shown to be the best enantiomer selector.In addition,the immobilized column packed with Chiralpak IA or IB was applied under polar-organic and reversed-phase conditions,both of which exhibited excellent enantioselectivity for Naftopidil and its derivatives.Furthermore,the underlying possible chiral recognition mechanisms were discussed.
基金supported by grants from the National Science Foundation of Guangdong Province (No. S2013040014088)the Postdoctoral Science Foundation of Guangzhou City (Q188)partially supported by the Guangdong Major Scientific and Technological Special Project for New Drug Development (2013A022100029)
文摘Chiral drug naftopidil(NAF), a specific α1D-adrenoceptor(AR) antagonist for the treatment of benign prostatic hyperplasia, was used in racemic form for several decades. Our recent work declared that NAF enantiomers showed the same antagonistic effects on the α1D-AR, but the binding mechanism of these two stereochemical NAF isomers to the α1D receptor remained unclear. Herein, we reported the crystallographic structures of optically pure NAF stereoisomers for the first time and unambiguously determined their absolute configurations. The crystal data of R and S enantiomers matched satisfactorily the pharmacophore model for α1D-selective antagonists. Based on the constructed α1D homology model,molecular docking studies shed light on the molecular mechanism of NAF enantiomers binding to α1D-AR. The results indicated that NAF enantiomers exhibited the very similar binding poses and occupied the same binding pocket.
文摘目的:探讨萘哌地尔(Naftop id il)治疗女性尿道综合征的有效性和安全性。方法:38例患者采用自身对照试验,洗脱期1周,治疗期4周,应用萘哌地尔片25mg,每晚口服。以尿道综合征症状评分(FUSS)为主要疗效指标,以生活质量评分(QOL)为次要观察指标。结果:治疗2周后患者症状开始好转,4周后疗效显著。治疗前后的FUSS、QOL相比较,差异显示均有统计学意义(P<0.01及P<0.05),总有效率为76.31%。结论:萘哌地尔治疗女性尿道综合征有效、安全。
