Mefunidone （MFD）, a pirfenidone analogue, has been suggested as a novel anti-fibrotic agent in preclinical research stage. In this work, we developed a sensitive and specified HPLC-UV method and validated it for the...Mefunidone （MFD）, a pirfenidone analogue, has been suggested as a novel anti-fibrotic agent in preclinical research stage. In this work, we developed a sensitive and specified HPLC-UV method and validated it for the determination of MFD in rat plasma. A cost-effective protein precipitation method using methanol was used to process the plasma samples, and pirfenidone was employed as the internal standard （IS）. Chromatographic separation was performed on an Agilent ZORBAX SB-Aq column （4.6 mm 250 mm, 5 μm） with a mobile phase consisting of 10 mM ammonium formate solution （pH 3.0, adjusted by 1.5%o formic acid）-acetonitrile-methanol （60：23：17, v/v/v） at a flow rate of 1.0 mL/min, and the samples were monitored at an ultraviolet wavelength of 245 nm. The retention times of MFD and IS were 5.5 and 7.8 min, respectively. The calibration curve was linear （r2 = 0.9997） between 0.1 and 20 pg/mL. The intra- and inter-day precisions were within 8.6%, and the bias of intra- and inter-accuracies of the method was between -4.2% and 6.5%. The method was successfully applied to pharmacokinetic study of MFD after i.g. and i.v. administration in rats. The elimination half-life was （3.41±0.81） h for i.g. administration and （2.26±0.87） h for i.v. administration. The absolute bioavailability of MFD in rat was 79.1%.展开更多
Novel anti-resistant liposomes have been developed to overcome intrinsic resistance in leukemia.Anticancer agent epirubicin and apoptotic inducer amlodipine were encapsulated into the liposome aqueous core,and the sur...Novel anti-resistant liposomes have been developed to overcome intrinsic resistance in leukemia.Anticancer agent epirubicin and apoptotic inducer amlodipine were encapsulated into the liposome aqueous core,and the surface of the liposome was modified using dequalinium.The objective of the present study was to establish a high performance liquid chromatography （HPLC） method for the determination of epirubicin,amlodipine and dequalinium in the liposomes.Analysis was performed on an ODS column with an isocratic elution at ambient temperature.Mobile phase was consisted of acetonitrile,0.02 M NaH_2PO_4 and triethylamine（34：66：0.3,v/v/v,pH 4.0）.The detection wavelength was set at 240 nm and the flow rate was 1.0 mL/min.The results showed that the calibration curves of epirubicin,amlodipine and dequalinium were linear in the range of（1-50）μg/mL（r^2= 0.9999）, respectively.The mean recoveries of epirubicin,amlodipine,and dequalinium were in the range of 95.86%-97.52%,97.17%-98.92% and 98.04%-101.13%,respectively.The contents of epirubicin,amlodipine and dequalinium in the liposomes were in the range of（564.2-606.1）μg/mL,（641.0-704.0）μg/mL,and（816.0-898.0）μg/mL,respectively.The encapsulation efficiencies of epirubicin and amlodipine were around 90%,and the modification rate of dequalinium was approximate 70μg/μmol lipids.The proposed HPLC method was simple and accurate for the simultaneous determination of epirubicin,amlodipine and dequalinium in newly developed anti-resistant liposomes.展开更多
基金National Natural Science Foundation of China(Grant No.81573498)supported by Nanxin Pharmaceutical Co.,Ltd.(Guangdong,China)
文摘Mefunidone （MFD）, a pirfenidone analogue, has been suggested as a novel anti-fibrotic agent in preclinical research stage. In this work, we developed a sensitive and specified HPLC-UV method and validated it for the determination of MFD in rat plasma. A cost-effective protein precipitation method using methanol was used to process the plasma samples, and pirfenidone was employed as the internal standard （IS）. Chromatographic separation was performed on an Agilent ZORBAX SB-Aq column （4.6 mm 250 mm, 5 μm） with a mobile phase consisting of 10 mM ammonium formate solution （pH 3.0, adjusted by 1.5%o formic acid）-acetonitrile-methanol （60：23：17, v/v/v） at a flow rate of 1.0 mL/min, and the samples were monitored at an ultraviolet wavelength of 245 nm. The retention times of MFD and IS were 5.5 and 7.8 min, respectively. The calibration curve was linear （r2 = 0.9997） between 0.1 and 20 pg/mL. The intra- and inter-day precisions were within 8.6%, and the bias of intra- and inter-accuracies of the method was between -4.2% and 6.5%. The method was successfully applied to pharmacokinetic study of MFD after i.g. and i.v. administration in rats. The elimination half-life was （3.41±0.81） h for i.g. administration and （2.26±0.87） h for i.v. administration. The absolute bioavailability of MFD in rat was 79.1%.
基金Beijing Natural Science Foundation(Grant No. 7091005)National Natural Science Foundation of China(Grant No.30772664)
文摘Novel anti-resistant liposomes have been developed to overcome intrinsic resistance in leukemia.Anticancer agent epirubicin and apoptotic inducer amlodipine were encapsulated into the liposome aqueous core,and the surface of the liposome was modified using dequalinium.The objective of the present study was to establish a high performance liquid chromatography （HPLC） method for the determination of epirubicin,amlodipine and dequalinium in the liposomes.Analysis was performed on an ODS column with an isocratic elution at ambient temperature.Mobile phase was consisted of acetonitrile,0.02 M NaH_2PO_4 and triethylamine（34：66：0.3,v/v/v,pH 4.0）.The detection wavelength was set at 240 nm and the flow rate was 1.0 mL/min.The results showed that the calibration curves of epirubicin,amlodipine and dequalinium were linear in the range of（1-50）μg/mL（r^2= 0.9999）, respectively.The mean recoveries of epirubicin,amlodipine,and dequalinium were in the range of 95.86%-97.52%,97.17%-98.92% and 98.04%-101.13%,respectively.The contents of epirubicin,amlodipine and dequalinium in the liposomes were in the range of（564.2-606.1）μg/mL,（641.0-704.0）μg/mL,and（816.0-898.0）μg/mL,respectively.The encapsulation efficiencies of epirubicin and amlodipine were around 90%,and the modification rate of dequalinium was approximate 70μg/μmol lipids.The proposed HPLC method was simple and accurate for the simultaneous determination of epirubicin,amlodipine and dequalinium in newly developed anti-resistant liposomes.
