Objective To study the pharmacokinetics of nitidine chloride（NC） in rat plasma after intragastrical（i.g.） administration. Methods A liquid chromatography-electrospray ionization-mass/mass sprectrometry（LC-ESI-MS...Objective To study the pharmacokinetics of nitidine chloride（NC） in rat plasma after intragastrical（i.g.） administration. Methods A liquid chromatography-electrospray ionization-mass/mass sprectrometry（LC-ESI-MS/MS） was used and carbamazepine was used as an intermal standard（I.S.）. The rat plasma samples were deproteinized with acetonitrile and the resultant supernatant was assayed on an analytical Diamonsil ^（TM）ODS C_（18） column（2.1 mm × 150 mm） equipped with a C_（18） guard column（4 mm × 20 mm） with a mobile phase of acetonitrile–10 mM ammonium acetate buffer–formic acid（35： 65： 0.2, v/v/v） at the flow rate of 0.25 mL/min. The LC–MS was carried out on a triple-quadrupole mass spectrometry equipped with an ESI and positive selected-ion monitoring. Target ions were monitored at [M-Cl]~＋ m/z 348.2 for NC and [M ＋ H]~＋ m/z237.2 for I.S., respectively. Results The simple one step deproteinize and rapid analysis method were successfully used in pharmacokinetic study on NC after i.g. administration. The linear relationship was good over the range of 2.5 – 1000.0 ng/ml（r^2 = 0.999 2） in rat plasma. The lower limit of quantification and detection were 2.5 and 1.6 ng/ml, respectively. The extraction recovery was in the range of 86.54 – 98.60%. The intra-and inter-day precisions（relative standard deviation） were less than 6.00%, with accuracies deviation between 89.40 to 95.57%. A two-compartment pharmacokinetic open model was proposed and validated to explain the apparent biphasic disposition of NC in rat plasma after i.g. administration. Conclusion This study was successfully applied to a pharmacokinetic study of NC in rats plasma following i.g. administration and could be used for preclinical and clinical pharmacokinetic evaluation of NC.展开更多
目的检测氯化两面针碱(NC)对人肝癌细胞基因表达情况的影响。方法建立人肝癌HepG2裸鼠移植瘤模型,应用基因芯片技术分析NC治疗肝癌后基因表达谱的改变,应用实时荧光定量PCR(Real time PCR)方法验证基因芯片结果。结果 NC能明显抑制人肝...目的检测氯化两面针碱(NC)对人肝癌细胞基因表达情况的影响。方法建立人肝癌HepG2裸鼠移植瘤模型,应用基因芯片技术分析NC治疗肝癌后基因表达谱的改变,应用实时荧光定量PCR(Real time PCR)方法验证基因芯片结果。结果 NC能明显抑制人肝癌裸鼠移植瘤的生长。NC组与生理盐水组比较,差异表达基因共有369个,其中上调基因183个,下调基因186个。与细胞凋亡、细胞周期相关的基因IHPK2、PR48、MTSS1等上调,Bcl 2L2、AMID、RTEL1 CCNT2等下调,Real time PCR结果显示基因表达的改变与芯片研究结果具有一致性。结论差异表达基因涉及细胞增殖与凋亡调控、细胞周期、肿瘤免疫相关、分裂/增殖、DNA损伤/修复等多个方面的功能。NC作用于肝癌的基因调控是一个多基因、多环节、多途径参与的过程。展开更多
基金Natural Science Foundation of Guangxi Province of China(2010GXNSFA013187)Chinese Medicine Science and Technology Development of Guangxi Administration of TCM Project(GZKZ1143)+1 种基金Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources(Guangxi Normal University)Ministry of Education of China(CMEMR2012-B01)
文摘Objective To study the pharmacokinetics of nitidine chloride（NC） in rat plasma after intragastrical（i.g.） administration. Methods A liquid chromatography-electrospray ionization-mass/mass sprectrometry（LC-ESI-MS/MS） was used and carbamazepine was used as an intermal standard（I.S.）. The rat plasma samples were deproteinized with acetonitrile and the resultant supernatant was assayed on an analytical Diamonsil ^（TM）ODS C_（18） column（2.1 mm × 150 mm） equipped with a C_（18） guard column（4 mm × 20 mm） with a mobile phase of acetonitrile–10 mM ammonium acetate buffer–formic acid（35： 65： 0.2, v/v/v） at the flow rate of 0.25 mL/min. The LC–MS was carried out on a triple-quadrupole mass spectrometry equipped with an ESI and positive selected-ion monitoring. Target ions were monitored at [M-Cl]~＋ m/z 348.2 for NC and [M ＋ H]~＋ m/z237.2 for I.S., respectively. Results The simple one step deproteinize and rapid analysis method were successfully used in pharmacokinetic study on NC after i.g. administration. The linear relationship was good over the range of 2.5 – 1000.0 ng/ml（r^2 = 0.999 2） in rat plasma. The lower limit of quantification and detection were 2.5 and 1.6 ng/ml, respectively. The extraction recovery was in the range of 86.54 – 98.60%. The intra-and inter-day precisions（relative standard deviation） were less than 6.00%, with accuracies deviation between 89.40 to 95.57%. A two-compartment pharmacokinetic open model was proposed and validated to explain the apparent biphasic disposition of NC in rat plasma after i.g. administration. Conclusion This study was successfully applied to a pharmacokinetic study of NC in rats plasma following i.g. administration and could be used for preclinical and clinical pharmacokinetic evaluation of NC.
文摘目的检测氯化两面针碱(NC)对人肝癌细胞基因表达情况的影响。方法建立人肝癌HepG2裸鼠移植瘤模型,应用基因芯片技术分析NC治疗肝癌后基因表达谱的改变,应用实时荧光定量PCR(Real time PCR)方法验证基因芯片结果。结果 NC能明显抑制人肝癌裸鼠移植瘤的生长。NC组与生理盐水组比较,差异表达基因共有369个,其中上调基因183个,下调基因186个。与细胞凋亡、细胞周期相关的基因IHPK2、PR48、MTSS1等上调,Bcl 2L2、AMID、RTEL1 CCNT2等下调,Real time PCR结果显示基因表达的改变与芯片研究结果具有一致性。结论差异表达基因涉及细胞增殖与凋亡调控、细胞周期、肿瘤免疫相关、分裂/增殖、DNA损伤/修复等多个方面的功能。NC作用于肝癌的基因调控是一个多基因、多环节、多途径参与的过程。
