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1.
指纹图谱的一种定性定量研究新方法:总量统计矩分析法   总被引:11,自引:0,他引:11  
本文运用了统计矩原理阐明并建立中药复方多成分指纹图谱定性定量分析法:总量统计矩方法。包括4个参数: ① 总零阶矩AUCT; ② 总响应率AUCPWT; ③ 总量一阶矩MCRTT,亦总量中心矩或总量平均保留时间,用T表示; ④ 总体二阶矩VCRTT,亦为平均保留时间方差,用2T表示。AUCT能用于中药复方指纹图谱定量分析,AUCPWT、MCRTT、VCRTT能用于中药复方指纹图谱定性分析。以此法研究不同产地大黄醇浸膏成分HPLC指纹图谱,得总量统计矩参数:AUCT为3.273×108 μV·s;AUCPWT为2.286×106 μV·s·mg-1;MCRTT为33.50 min; VCRTT为484.4 min2;浓度CT为143.2 mg·mL-1。本法具有加合运算的特征,能消除溶剂干扰,获得纯品的总量统计矩参数;具偶联性,能与多维向量偶联构成多维曲线中心矩及偏差分析。  相似文献   

2.
目的:建立注射用双黄连(冻干)的UPLC指纹图谱并用于评价不同批次双黄连冻干粉。方法:采用ACQUITY UPLC RHSS T3色谱柱;以乙腈与0.2%甲酸水为流动相;柱温室温;进样量5μL;流速0.2 mL﹒min-1,梯度洗脱;检测波长350 nm。收集并制备双黄连冻干粉不同样品,采用相似度分析及聚类分析区分不同的双黄连冻干粉样品。结果:标定了正常双黄连冻干粉样品的26个共有峰,并结合对照品比对确定了其中11个成分。通过聚类分析,所有特殊双黄连冻干粉样品均可以与正常样品区分。结论:所建立的UPLC指纹图谱具有快速、高效的特点,可用于双黄连冻干粉的质量检测。  相似文献   

3.
目的 建立舒眠胶囊HPLC-ELSD指纹图谱与化学计量学相结合,全面、系统评价舒眠胶囊质量的方法。方法 采用ACE Excel AR C18色谱柱(4.6 mm×250 mm,5.0 μm),流动相为乙腈-水,梯度洗脱,柱温30℃,流速为1.0 mL·min-1,ELSD漂移管温度50℃,N2流速为3.0 mL·min-1。用HPLC-ELSD对15批次舒眠胶囊进行分析,建立指纹图谱共有模式,采用聚类分析(cluster analysis,CA)、主成分分析(principal component analysis,PCA)等化学计量学方法进行区分与比较,寻找导致不同批次间差异的主要标志性成分。结果 共确定了16个共有峰,归属了10个共有峰的药材来源,通过对照品比对指认了4个共有峰归属,分别为柴胡皂苷a、芍药内酯苷、芍药苷、槲皮苷,样品相似度均>0.90,CA将样品分为3类,PCA筛选出不同批次间差异的主要标记物,分别为3(芍药苷),14,15号峰。结论 本研究建立的HPLC-ELSD指纹图谱与HPLC-DAD指纹图谱相结合能对舒眠胶囊产品一致性、稳定性进行全面有效评价,可用于舒眠胶囊的质量综合评价。  相似文献   

4.
诺氟沙星注射剂和胶囊剂的人体药代动力学   总被引:1,自引:0,他引:1  
栾立标  朱家壁 《药学学报》2000,35(2):147-150
目的:考察自制的肌注诺氟沙星注射剂在体内的动态行为,并与诺氟沙星胶囊剂进行比较。方法:用HPLC法测定这两种制剂在人体的血药浓度,并用非线性最小二乘法迭代程序进行数据处理。结果:注射剂在体内的过程可用开放型二室模型描述,其主要体内参数为:AUC=5.84 h.μg.mL-1,Tmax=0.35 h,Cmax=1.14 μg.mL-1,MRT=7.32 h;而胶囊剂则符合一室模型,主要体内参数为:AUC=4.29 h.μg.mL-1,Tmax=1.28 h,Cmax=0.72 μg.mL-1,MRT=6.16 h。结论:注射剂较胶囊剂生物利用度高,起效快,峰浓度高,作用持久。  相似文献   

5.
目的建立注射用双黄连冻干粉指纹图谱的高效液相色谱分析方法,并对10批注射用双黄连进行相似性评价。方法采用C18(150mm×4.6mm,5μm)色谱柱,流动相为甲醇-0.25%冰醋酸,流速为1.0ml/min,检测波长350nm,柱温30℃,梯度洗脱的方法进行色谱分离。结果得到注射用双黄连及其对照品的指纹图谱,并对10批样品进行相似性评价,结果>0.97。结论 10批产品质量稳定,指纹谱检测方法简便、可靠,可用于注射用双黄连的质量控制及进一步安全性研究。  相似文献   

6.
目的 建立注射用益气复脉(冻干)的HPLC指纹图谱,并建立评价其质量的指纹图谱分析方法。方法 采用HPLC法,色谱柱为Waters Symmetry® C18柱(250 mm×4.6 mm,5 μm);流动相为乙腈-0.01%磷酸水溶液梯度洗脱;检测波长203 nm;柱温32 ℃。结果 建立了注射用益气复脉(冻干)中人参皂苷类、五味子木质素类的指纹图谱,并建立了3种指纹图谱分析评价方法。结论 建立的注射用益气复脉(冻干)指纹图谱的重复性、稳定性好,采用夹角余弦法与相关系数法从两个不同的角度评价指纹图谱,可以有效地反映益气复脉的质量,两者差异不大,而采用欧氏距离法却无法获得两张图谱的真实相似程度,无法给出直观的综合质量评价结果。  相似文献   

7.
黄芩药材指纹图谱研究   总被引:1,自引:0,他引:1       下载免费PDF全文
张振巍  张娜娜  石磊  李月梅 《中国药师》2013,(10):1449-1451
摘 要 目的: 建立院内制剂生产采购黄芩药材的HPLC指纹图谱分析方法,为制剂内在质量评价积累数据。方法: 采用HPLC方法,以SHIMADZU VP-ODS C18色谱柱(150 mm×4.6 mm,5 μm);流动相甲醇-0.2%磷酸水(47∶53)等度洗脱;检测波长为280 nm;柱温为30℃;流量为1.0 ml·min-1,进样量:5 μl。结果:建立黄芩药材指纹图谱,以5号色谱峰黄芩苷为参照峰,确定10个共有峰,测定了11批样品,样品指纹图谱相似度均大于0.8。结论:从整体上显示了购进的不同批次黄芩药材成分特征变化趋势,建立的HPLC指纹图谱方法为含黄芩的院内制剂质量控制提供有效手段。  相似文献   

8.
目的 考察建立咽喉清口含片高效液相色谱(HPLC)特征图谱质量控制方法。方法 采用高效液相色谱法,色谱柱为Waters Symmetry C18柱(4.6 mm×250 mm,5 μm),流动相为乙腈-0.4%磷酸水溶液,梯度洗脱,检测波长为260 nm,流速为1.0 mL·min-1,柱温为30 ℃,测定10批次咽喉清口含片样品,并将所获得的色谱图导入国家药典委员会颁布的“中药色谱指纹图相似度评价系统(2012版)”,经过多点校正和数据匹配生成色谱特征图谱共有模式,计算各批次样品图谱与标准图谱的相似度,并以色谱图中绿原酸峰为参照峰,计算各色谱峰相对保留时间。结果 得到咽喉清口含片特征图谱共有模式,确认了20个共有特征峰。结论 经过方法学验证,所建立方法稳定可行,可用于咽喉清口含片的质量控制。  相似文献   

9.
胸腺肽α1缓释注射微球的研究   总被引:2,自引:0,他引:2  
朱艳  鲁莹  钟延强 《药学学报》2007,42(2):211-215
制备胸腺肽α1(Tα1)的长效注射微球,并对微球的体外释放特性、体外活性及药效学进行考察。采用复乳法(W/O/W)制备了载Tα1聚乳酸-羟基乙酸嵌段共聚物(PLGA)的微球;考察微球的粒径大小、外观及包封率等理化特性;以HPLC法测定微球的体外释放速率;采用CCK-8法评价微球制备工艺和体外释放过程中Tα1的生物学活性;体内药效学研究中采用流式细胞仪检测免疫抑制模型大鼠给予Tα1微球后所产生的CD4+,CD8+因子的量,根据CD4+/CD8+的比值变化评价体内药效。微球球形圆整,分散性好,两个优选处方(外水相中加入5%氯化钠和10%葡萄糖)的微球包封率分别为87.8%和90.2%;Tα1微球1个月的体外累积释放可达90%以上。使用含10%葡萄糖的PVA溶液作为外水相,较好地保持了制备工艺过程中的Tα1生物学活性,在体外释放过程中Tα1的生物学活性略有下降;Tα1微球可显著提高免疫抑制模型小鼠的免疫力。用可生物降解的聚合物PLGA作为载体材料,可以将Tα1制备成缓释1个月的注射微球。  相似文献   

10.
胡亮  周明  丁野  罗疆南  孙辉 《药学研究》2023,42(3):170-175
目的 建立肾石通颗粒UPLC特征图谱,并对不同生产企业样品进行初步评价。方法 样品采用80%甲醇超声提取,以CAPCELL PAK C18 (2.1 mm×150 mm,2 μm)为色谱柱,以乙腈-0.1%磷酸溶液作为流动相进行梯度洗脱,流速0.2 mL•min-1,柱温35 ℃,检测波长280 nm,进样量2 μL。结果 对收集的222批次样品进行分析,通过《中药色谱指纹图谱相似度评价系统》(2012年版)建立了肾石通颗粒UPLC特征图谱,共确定了15个特征峰,可归属至丹参、牛膝、萹蓄、王不留行、海金沙、鸡内金、瞿麦、金钱草共八味药材,结果表明不同企业间样品相似度差异较大,11批次样品相似度低于0.85,可能存在投料药材质量参差不齐、生产工艺稳定性欠佳等问题。结论 该研究建立的特征图谱方法便捷、准确,大幅缩短了分析时间、节约了溶剂,提高了分析效率,为肾石通颗粒质量整体评价提供了依据。  相似文献   

11.
星点设计-效应面法优化双嘧达莫漂浮渗透泵给药系统   总被引:2,自引:0,他引:2  
本文设计了双嘧达莫气囊式漂浮渗透泵。采用中国药典 (2005版) 附录XD释放度测定法第三法装置同时评价制剂的体外释放和漂浮性能。以聚氧乙烯 (PEO WSR303) 用量 (X1, mg)、NaCl用量 (X2, mg) 和致孔剂用量 (PEG4000, X3, %) 为自变量, 自制处方溶出曲线与目标溶出曲线相比而得的相似因子 (f2) 为应变量, 采用星点设计-效应面法优化系统。优化模型为
(R = 0.996), 当包衣 增重8%~9%、X1: 20~34、X2: 30~57、X3: 50时溶出曲线和目标溶出曲线相似, 从优化模型可得致孔剂用量最小值为35.1%, 所得优化模型在试验范围内预测效果良好。  相似文献   

12.
The effect of various psychotropic drugs on the ambivalent behaviour stretched approach posture (SAP) in the rat was assessed. SAP was elicited after a mild startle reaction due to physical contact with an electrified prod at one end of a straight runway. Using ethological observation methods, SAP as well as intention movements, prod contact, crossings, rearing, exploration, grooming and immobility were recorded. The benzodiazepine receptor agonists chlordiazepoxide, diazepam and alprazolam, the 5-HT1A receptor agonists flesinoxan and ipsapirone and the 5-HT uptake inhibitor clomipramine selectively (no effect on crossings) reduced SAP. Except for alprazolam, these drugs also reduced intention movements. In addition, chlordiazepoxide and diazepam enhanced prod contact. Reductions of SAP and intentions with concomitant reductions of crossings (nonspecific anti-ambivalent effects) were established for the 2-adrenoceptor agonist clonidine and the MAO inhibitor clorgyline. The 5-HT uptake inhibitor fluvoxamine suppressed intention movements, but not SAP. The mixed 5-HT/NA uptake inhibitor imipramine did not significantly affect SAP or intentions, but reduced crossings. The 5-HT2C/1B receptor agonist m-CPP, the inverse BZD receptor agonists FG 7142 and DMCM, and the 2-adrenoceptor antagonist yohimbine, to all of which putative anxiogenic effects have been ascribed, had no effect on SAP directed towards the prod. m-CPP, however, produced an increase in the stretched posture directed away from the prod (SAwayP). FG 7142 reduced intentions while strongly enhancing immobility (freezing). SAwayP and/or freezing may possibly reflect anxiogenic properties of drugs. The putative anxiogenic drug pentylenetetrazol false positively reduced SAP while increasing exploration. The dopamine-D2 receptor antagonist haloperidol and the catecholamine releaserdl-amphetamine had no effect on ambivalent behaviour. The muscarine receptor antagonist scopolamine reduced SAP and intentions while stimulating crossings. Finally, the 5-HT2C receptor antagonist ritanserine, the CCKA receptor antagonist devazepide, the CCKB receptor antagonist L-365.260 and the strychnine-insensitive glycine site antagonist 7-Cl-kynurenic acid were without effect on the behaviours in this paradigm using single doses. In conclusion, SAP and intention movements were reduced selectively by anxiolytic agents from different classes, including benzodiazepine receptor agonists, 5-HT1A receptor agonists and a 5-HT uptake inhibitor, whereas an 2-adrenoceptor agonist and a MAO inhibitor reduced SAP non-selectively. SAP in relation to other behaviours may therefore serve as a valuable paradigm to characterize anxiolytic drugs.  相似文献   

13.
The effect of a diffusional barrier to a metabolite between the blood and hepatocytes on elimination kinetics of formed and preformed metabolites was predicted under various enzymic distributions in the liver by computer- aided simulation. Sequential metabolism by which the primary metabolite (MI) is generated from the parent drug (D) and further metabolized to the terminal metabolite (MII) by enzymes A and B, respectively, was chosen for the simulation. Moreover, four models of enzymic distribution patterns were defined with regard to the hepatic blood flow path. The extraction ratios for the preformed and formed metabolites (designated as Em and Epm, respectively) were simulated by varying both the average intrinsic clearance of enzyme B ( ) and the permeability of hepatocytes for MI ( ), while keeping the average intrinsic clearance of enzyme A ( ) equal to hepatic blood flow (Q). When a rapid equilibrium of MI between the blood and hepatocytes held, i.e., was large relative to Q, Em was equal to or higher than Epm for all models, as previously shown by Pang and Stillwell. By contrast, it was found that when a diffusional barrier for MI existed, i.e., was small relative to Q, Em was equal to or lower than Epm. Furthermore, it was observed that the smaller became, the larger the difference between Em and Epm became. We further simulated the effect of the intrinsic clearance ( ) for a metabolic pathway, which competes for that by enzyme A. on the E pm value. In the model assuming even distribution of all the enzymes along the flow path, irrespective of the value, a similar effect of on Epm was observed when the value was relatively small ( ). By contrast, in the case of uneven enzymic distributions of enzymes A and B, the effect of the value on the relationship between Pm and Epm occurred to some extent. From these simulations, it was concluded that lower membrane permeability ( ) both diminishes the entry of preformed metabolite into the hepatocytes and accelerates the removal of intracellularly formed metabolite (through sequential metabolism) by diminishing its efflux, yielding lower Em than Epm. When becomes small ( ), these mechanisms for lower Em than Epm predominate over other mechanisms such as the presence of a competing metabolic route and uneven distribution of enzymes.  相似文献   

14.
Based on a generalized model, equations for calculating the mean residence time in the body at single dose (MRT) and at steady state (MRT ss), apparent steady-state volume of distribution ( ) and steady-state volume of distribution (V ss) are derived for a drug exhibiting nonlinear protein binding. Interrelationships between andV ss as well as betweenMRT andMRT ss are also discussed and illustrated with simulated data. In addition, a method for estimating the central volume of distribution of the bound drug and the sum of the central volume of distribution of the unbound drug and the area under the first moment curve of distribution function for drugs with nonlinear protein binding is proposed and illustrated with both simulated and published data.  相似文献   

15.
Purpose  We compared the pharmacokinetics of chloroquine in pregnant and nonpregnant women treated for Plasmodium vivax malaria. Methods  Twelve pregnant women and 15 nonpregnant women of child-bearing age with acute P. vivax malaria were treated with 25 mg chloroquine base/kg over 3 days on the northwestern border of Thailand. Blood concentrations of chloroquine and desethylchloroquine were measured using hydrophilic interaction liquid chromatography coupled with fluorescence detection. Twenty-five women completed the pharmacokinetic study. Results  Although increasing gestational age was associated with reduced chloroquine , there was no significant difference overall in the pharmacokinetics of chloroquine between pregnant and nonpregnant women. Fever was associated with lower chloroquine values. Desethylchloroquine area under the curve (AUC) values were not significantly affected by pregnancy. Conclusions  Pregnancy did not significantly affect blood concentrations of chloroquine or its metabolite, desethylchloroquine, in women with P. vivax malaria.  相似文献   

16.
Summary In the isolated rat vas deferens stimulated at 0.2 Hz, [14C]labelled 5-AMP, 5-ADP and 5-ATP (10 M) inhibited twitch responses, were broken down to [14C]adenosine in the medium and incorporated into [14C]adenine ribonucleotides in the tissue. Pretreatment of tissues with 6-(2-hydroxy-5-nitrobenzyl)-thioguanosine (NBTGR), a potent inhibitor of adenosine transport, potentiated the presynaptic inhibitory action of these 5 nucleotides and reduced their incorporation in [14C]adenine nucleotides, but did not alter the appearance of [14C]adenosine in the medium.A series of 2, 3 and 5-substituted adenine nucleotides (10 M) inhibited the twitch responses of the vas deferens stimulated at 0.2 Hz. This effect was potentiated by NBTGR. Addition of exogenous adenosine deaminase very significantly reduced the inhibitory actions of adenosine, 5-AMP, 5-ADP and 5-ATP and also reduced those of 2, 5-ADP, NAD+ and dePCoA. The inhibitory actions of the other 2, 3 and 5 adenine nucleotides studied were not altered by exogenous adenosine deaminase.These results indicated that the presynaptic inhibitory actions of 5-AMP, 5-ADP and 5-ATP in rat vas deferens predominantly result from their prior hydrolysis to adenosine whereas the 2, 3 and 5-substituted adenine nucleotides appear to act mainly directly to inhibit transmitter release.Abbreviations. The following abbreviations are used 5-ADP 5-adenosine diphosphate - 2,5-ADP 2,5-adenosine diphosphate - 3,5-ADP 3,5-adenosine diphosphate - 2,3 or 5-AMP 2,3 or 5-adenosine monophosphate - 5-ATP 5-adenosine triphosphate - CoA coenzyme A - 2,3-cAMP 2,3-cyclic adenosine monophosphate - cNADP+ -nicotinamide dinucleotide 2,3-cyclic monophosphate - dePCoA dephosphocoenzyme A - NAD+ -nicotinamide adenine dinucleotide - NADP+ -nicotinamide adenine dinucleotide phosphate - NBTGR 6-(2-hydroxy-5-nitrobenzyl)-thioguanosine - oxid CoA oxidized-coenzyme A  相似文献   

17.
Purpose  To investigate the effects of silymarin on the pharmacokinetics of losartan and its active metabolite E-3174 and its relationship with CYP2C9 genotypes. Methods  Twelve healthy adult men of known CYP2C9 genotype (six CYP2C9*1/*1 and six CYP2C9*1/*3) were recruited in a two-phase randomized crossover design study. The pharmacokinetics of losartan and E-3174 were measured before and after a 14-day treatment with 140 mg of silymarin three times daily. Results  The area under the plasma concentration–time curve (AUC) of losartan increased significantly following a 14-day silymarin treatment in subjects with the CYP2C9*1/*1 genotype, but not in those with the CYP2C9*1/*3 genotype. The AUC of E-3174 decreased significantly with a silymarin pretreatment in both CYP2C9*1/*1 and the CYP2C9*1/*3 subjects. The metabolic ratio of losartan (ratio of of E-3174 to of losartan) decreased significantly after a 14-day treatment with silymarin in individuals with the CYP2C9*1/*1 genotype (p < 0.05), but not in those with the CYP2C9*1/*3 genotype (p = 0.065). Conclusion  Silymarin inhibits the metabolism of losartan to E-3174, with the magnitude of the interaction differing in individuals with different CYP2C9 genotypes.  相似文献   

18.
Objective  To investigate the interaction between allicin and omeprazole and to observe the effects of allicin on CYP2C19 and CYP3A4 activity in healthy Chinese male volunteers with different CYP2C19 genotypes. Methods  Eighteen subjects (six CYP2C19*1/CYP2C19*1, four CYP2C19*1/CYP2C19*2, two CYP2C19*1/ CYP2C19*3, and six CYP2C19*2/ CYP2C19*2) were enrolled in a two-phase randomized crossover trial. In each phase, all subjects received placebo or a 180 mg allicin capsule once daily for 14 consecutive days. The pharmacokinetics of omeprazole (20 mg orally on day 15) was determined for up to 12 h following administration by high-performance liquid chromatography. Results  In carriers of the CYP2C19*1/CYP2C19*1 and CYP2C19*1/CYP2C19*2 or *3 genotype, allicin treatment increased the peak plasma concentration (Cmax) of omeprazole by 49.7 ± 7.2 (p < 0.001) and 54.2 ± 9.2% (p < 0.001), and increased the area under the plasma time–concentration curve ( ) of omeprazole by 48.1 ± 9.0 (p = 0.001) and 73.6 ± 26.7% (p < 0.001), respectively. The ratio of of 5-hydroxyomeprazole to omeprazole (a marker for CYP2C19 activity) decreased significantly (p < 0.001 and p = 0.001, respectively). However, no pharmacokinetic parameters were significantly changed by allicin in CYP2C19*2/CYP2C19*2. The Cmax and of omeprazole sulfone were unchanged in all three genotypes. Conclusions  Allicin reduced the metabolism of omeprazole by inhibiting CYP2C19 activity in individuals with the CYP2C19*1/CYP2C19*1 and CYP2C19*1/CYP2C19*2 or *3 genotypes, but not in those with the CYP2C19*2/ CYP2C19*2 genotype. Allicin did not significantly affect the activity of CYP3A4 in all subjects.  相似文献   

19.
The plasma concentration vs. anesthetic effect relationships for ketamine are not well known. It is desirable to establish stable and predictable drug concentrations in plasma (and brain) in order to define such relationships. As a prelude to pharmacodynamic studies, we investigated ketamine pharmacokinetics in eight dogs anesthetized with enflurane and correlated ketamine concentration in plasma (KET) with its ability to reduce the enflurane concentration required for anesthesia (enflurane EC50: MAC-the endtidal concentration at which half the dogs moved in response to damping of the tail and half did not move). Four dogs (Group 1) received ketamine 10 mg/kg iv over 30 sec. Blood for determination of KET was collected repeatedly over the 5-h period following injection. Based on the pharmacokinetic parameters determined for Group I, four dogs in Group 2 received ketamine as a continuous infusion of 300 g·kg–1·min–1 for 5hr accompanied by an initial loading dose (26 mg/kg administered over 20 min) designed to produce a stable KET of 20 g/ml of plasma. Enflurane MAC and KET were determined regularly during the infusion and for 5 hr after discontinuation of the infusion. There were no significant differences in the following pharmacokinetic parameters determined for Group 1 vs. Group2: =122±9 vs. 141±40min ( ±SD) and CL±8.1±5.9 vs. 13.9±2.5ml·kg–1min–1, respectively. When administered as a continuous infusion (Group 2), KET remained relatively stable at 22.1±4.6 g/ml for 5hr. The degree of MAC reduction remained relatively stable at 73% during the continuous infusion. Finally, the enflurane MAC reduction vs. KET was established over a wide range of plasma concentrations in 4 additional dogs (Group 3). This study determined that the pharmacokinetics of ketamine were consistent under two different experimental conditions and demonstrated the relationship between plasma concentration and anesthetic effect in the dog.Supported in part by a grant from the Swiss National Fund.  相似文献   

20.
Zusammenfassung Zur Auftrennung von sechs therapeutisch verwendeten Salicylamidderivaten auf Kieselgelschichten werden Chloroform/Äther/Aceton (602020) und Chloroform/Benzol/Aceton (602020) als Mie\mittel benutzt. Zum Nachweis dieser Substanz sind u.a. Eisen(III)-chlorid und 2,6-Dibromchinonchlorimid verwendet worden.Herrn Prof. Dr. Dr. E.Weinig zum 65. Geburtstag gewidmet.  相似文献   

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