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1.
目的 建立同时测定沙芬酰胺原料药中5种磺酸酯类基因毒性杂质(甲磺酸甲酯、甲磺酸乙酯、甲磺酸异丙酯、甲磺酸丙酯、甲磺酸丁酯)的方法。方法 采用顶空进样气相色谱-质谱联用法,在线衍生,RESTEK Rxi-624Sil毛细管柱(30 m×0.25 mm,1.4 μm),四级杆质量检测器,离子化模式为电子轰击离子化(EI)模式,采集模式为选择离子监测。结果 5种杂质检测限为0.3~1.3 ng·mL-1,定量限为0.9~4.3 ng·mL-1;精密度、稳定性、重复性试验的RSD均<5%;浓度在5~300 ng·mL-1内,5种杂质的峰面积与其相对应的浓度有良好的线性关系,相关系数(r2)均>0.995;回收率为99.4%~100.6%,RSD为0.8%~2.6%(n=9)。结论 该法操作简便,重复性好,结果准确可靠,可用于沙芬酰胺中磺酸酯类基因毒性杂质的测定。  相似文献   

2.
目的 采用LC-MS/MS测定患者血浆中莫西沙星浓度,并进行血药浓度监测。方法 血浆样品用乙腈沉淀蛋白后,以普瑞巴林为内标,选用ZORBAX SB C18(2.1 mm×100 mm,3.5 μm)色谱柱,以乙腈-水(均含0.1%甲酸)为流动相梯度洗脱,流速为0.30 mL·min-1,柱温为30℃,进样量为10 μL,总分析时间为4.0 min;采用电喷雾离子化源,正离子方式,多反应监测扫描方式进行监测。结果 血浆中莫西沙星浓度线性范围为10~5 000 μg·mL-1r=0.997 8),定量下限为10 ng·mL-1;质控样品准确度为94.2%~107.1%;日内、日间RSD<15%;样品和内标提取回收率在82.4%~89.8%。结论 该方法快速、灵敏、准确,专属性强,重复性好,适用于莫西沙星临床血药浓度测定。  相似文献   

3.
目的 建立LC-MS/MS方法测定酒石酸溴莫尼定中苯胺类基因毒性杂质(6-氨基喹喔啉、4-硝基邻苯二胺、6-氨基-5-溴喹喔啉)的含量。方法 采用色谱柱ZORBAX Eclipse Plus C18(2.1 mm×50 mm,1.8 μm),流动相为0.1%乙酸水溶液(A)-乙腈(B),梯度洗脱,流速0.35 mL·min-1,柱温为35℃;采用Shimadzu LC30 UPLC-AB Science 4000+三重四极杆液质联用仪和多反应离子监测模式二级质谱MS/MS(ESI)源检测,正离子模式采集数据。结果 6-氨基喹喔啉、4-硝基邻苯二胺、6-氨基-5-溴喹喔啉分别在9.98~199.50,9.94~198.74,10.03~200.55 ng·mL-1内线性关系良好;低、中、高浓度(50,100,150 ng·mL-1)回收率为94.8%~110.8%,RSD均<4.2%;溶液在12 h内稳定性良好。结论 本方法操作简便,结果可靠,可以用于酒石酸溴莫尼定中苯胺类基因毒性杂质(6-氨基喹喔啉、4-硝基邻苯二胺、6-氨基-5-溴喹喔啉)的控制。  相似文献   

4.
目的 采用与静脉注射对比的方式,研究聚乙二醇-聚乳酸-α-细辛脑纳米粒(PEG-PLA-α-细辛脑纳米粒)鼻腔给药后在大鼠体内的药物动力学。方法 以大鼠为动物模型,采用血药动力学、脑药动力学及荧光标记法对比研究PEG-PLA-α-细辛脑纳米粒经鼻腔给药与静脉注射后药物/纳米粒在大鼠体内的分布情况。结果 PEG-PLA-α-细辛脑纳米粒静脉注射及鼻腔给药后血浆中的AUC(0-∞)分别为(11032.4±1 827.1)ng·mL-1·min及(5 992.9±717.5)ng·mL-1·min,Cmax分别为(421.9±100.2)ng·mL-1及(171.7±26.3)ng·mL-1,PEG-PLA-α-细辛脑纳米粒鼻腔给药后的绝对生物利用度F为54.3%。PEG-PLA-α-细辛脑纳米粒静脉注射后α-细辛脑在脑组织中的Cmax与鼻腔给药后α-细辛脑在脑组织中的浓度Cmax分别为(217.9±29.9)ng·mL-1及(334.2±62.7)ng·mL-1,PEG-PLA-α-细辛脑纳米粒静脉注射与鼻腔给药后的AUCbrain/AUCplasma值分别为1.37和2.85,且两者具有统计学意义。PEG-PLA-α-细辛脑纳米粒鼻腔给药后的药物脑靶向效率及鼻-脑传递百分比分别为208.03%及52.01%。荧光标记法结果显示,PEG-PLA-α-细辛脑纳米粒鼻腔给药后脑靶向性比静脉注射后更强。结论 PEG-PLA-α-细辛脑纳米粒适合于鼻腔给药治疗脑部疾病。  相似文献   

5.
目的 建立HPLC测定异维A酸有关物质的方法。方法 色谱柱为NUCLEOSIL 100-3 C18(4.6 mm×150 mm,3 μm),以甲醇-水-冰醋酸(770:225:5)为流动相,流速为1.0 mL·min-1;柱温为25℃,检测波长为355 nm。结果 异维A酸峰与杂质H、I、维A酸、强制降解杂质峰分离良好;异维A酸、杂质H、I和维A酸的线性范围分别为0.000 545 5~21.82 μg·mL-1r=0.999 9),0.002 856~7.14 μg·mL-1r=0.999 0),0.002 789~6.97 μg·mL-1r=0.999 1)、0.017 07~22.76 μg·mL-1r=0.999 6);检测限分别为0.27,0.60,0.65,5.50 ng·mL-1,定量限分别为0.55,2.85,2.80,17.00 ng·mL-1;杂质H、I和维A酸的平均回收率分别为101.57%,102.02%,101.03%,RSD分别为0.5%,0.8%,1.5%。结论 建立的HPLC方法准确、专属性强,可用于异维A酸有关物质的测定。  相似文献   

6.
目的 建立大鼠血浆中青蒿琥酯的HPLC-MS/MS测定方法,并研究青蒿琥酯自微乳在大鼠体内的药动学特征。方法 12只SD大鼠随机分为2组,单剂量分别灌胃(50 mg·kg-1)青蒿琥酯自微乳和青蒿琥酯原料药,以格列吡嗪为内标,用LC-MS/MS测定给药后血浆中的药物浓度,并计算药动学参数。结果 青蒿琥酯血浆样品的线性范围为1.0~1 000.0 ng·mL-1,回归方程为A=294.74C-439.33(r=0.999 6),定量下限为1.0 ng·mL-1。日内、日间变异系数(RSD)均<10%,符合生物样品的分析要求。青蒿琥酯原料药和青蒿琥酯自微乳的药动学参数Cmaxt1/2和AUC0→t分别为:(87.6±8.80)ng·mL-1,(1.88±0.33)h和(43.3±1.74)h·ng·mL-1;(421±41.6)ng·mL-1,(1.48±0.17)h和(282±17.7)h·ng·mL-1。其中,Cmax和AUC0→t存在显著性差异(p<0.01)。结论 该方法简便灵敏,可用于血浆中青蒿琥酯的含量测定,经灌胃给药后,与原料药比较,青蒿琥酯自微乳能显著提高生物利用度。  相似文献   

7.
目的 采用顶空进样气相色谱三重四级杆质谱联用(HS-GC-MS/MS)法测定富马酸丙酚替诺福韦中微量的基因毒性杂质N-亚硝基二甲胺(NDMA)。方法 采用三重四极杆GC-MS/MS,Agilent VF-WAX ms(30 m×0.25 mm,1 μm)色谱柱,载气:氦气;恒流模式1.0 mL·min-1;程序升温,进样口温度230℃,顶空温度130℃;质谱采用电子轰击电离源(EI),电离能量为70 eV,离子源温度230℃,多反应监测(MRM)模式进行检测,溶剂为N-甲基吡咯烷酮(NMP)。进行专属性、系统适用性、检测限与定量限、线性与范围、准确度、精密度、溶液稳定性、耐用性考察。结果 NDMA与相邻色谱峰之间分离效果良好;NDMA在7.0~105.0 ng·mL-1线性关系良好,检测限为3.5 ng·mL-1,定量限为7.0 ng·mL-1;NDMA低、中、高质量浓度(56、70、84 ng·mL-1)回收率为95.6%~109.3%,RSD为4.0%(n=9);重复性试验NDMA质量浓度RSD为6.5%,中间精密度RSD为6.1%;对照品溶液室温放置24 h稳定,供试品溶液室温放置90 h内溶液稳定;保持其他条件不变,分别改变进样口温度(230、225、235℃)、离子源温度(230、225、235℃)、载气体积流量(1.0、0.9、1.1 mL·min-1)、顶空温度(130、128、132℃),方法耐用性良好。结论 所建立的方法准确度好、灵敏度高、简便可靠,对仪器污染小,可用于富马酸丙酚替诺福韦中NDMA的质量控制。  相似文献   

8.
目的 建立测定盐酸莫西沙星中侧链的方法。方法 采用柱前衍生反相高效液相色谱(HPLC)法,采用C18 (4.6 mm×250 mm,5 µm) 色谱柱,以0.1%三乙胺溶液(用磷酸调节pH值至7.5)-乙腈(50:50)为流动相,流速为1.0 mL·min-1,检测波长为245 nm。结果 盐酸莫西沙星侧链在0.210~1.577 µg·mL-1浓度范围内呈良好的线性关系,检测限为0.013 µg·mL-1,定量限为0.042 µg·mL-1,加标回收率为102.8%~106.2%。结论 该方法简单快速,专属性强,准确度好,灵敏度高。  相似文献   

9.
目的 评价中国健康受试者空腹和餐后状态下单次口服盐酸二甲双胍缓释片的生物等效性。方法 采用单剂量、随机、开放、两制剂、两周期、交叉对照的试验设计,健康受试者每周期在空腹或餐后状态下口服盐酸二甲双胍缓释片受试制剂和参比制剂500 mg。采用经验证的液相色谱-串联质谱(LC-MS/MS)法测定二甲双胍的血浆浓度,使用Phoenix WinNonlin 8.0计算药动学参数并用SAS9.4软件进行生物等效性评价。结果 空腹状态下,受试制剂和参比制剂中二甲双胍Cmax分别为(733.00±178.25)、(665.80±146.58) ng·mL-1,AUC0~t分别为(4 848.60±1 204.80)、(4 743.00±1 104.34) h·ng·mL-1,AUC0 ~ ∞分别为(4 940.70±1 219.48)、(4 832.58±1 093.55) h·ng·mL-1。餐后状态下,受试制剂和参比制剂中二甲双胍Cmax分别为(519.10±92.55)、(475.50±65.88) ng·mL-1,AUC0~t分别为(5 989.20±1 112.01)、(5 946.50±1 094.81) h·ng·mL-1,AUC0 ~ ∞分别为(6 052.20±1 118.35)、(6 049.80±1 062.28) h·ng·mL-1。受试制剂和参比制剂二甲双胍Cmax、AUC0~t和AUC0~∞几何均值比的90%置信区间均在80.00%~125.00%的生物等效性范围内。结论 盐酸二甲双胍缓释片受试制剂和参比制剂在空腹和餐后状态下均具有生物等效性。  相似文献   

10.
目的 建立同时测定大鼠血浆中芦丁和氢氯噻嗪的LC-MS/MS方法,并研究珍菊降压片在大鼠体内的药动学。方法 采用蛋白质沉淀法处理血浆样品,色谱柱为Pntulips BP-C18柱(2.1 mm×50 mm,5μm),流动相为乙腈-水梯度洗脱,柱温为30℃;流速为0.45 mL·min-1。采用电喷雾离子源,选择离子反应监测模式。采用DAS 2.0软件计算药动学参数。结果 方法学验证结果表明内源性杂质不干扰待测物和内标的测定,芦丁和氢氯噻嗪的线性范围分别为5~1 000 ng·mL-1r2=0.997 1)和2.5~500 ng·mL-1r2=0.995 8)。芦丁和氢氯噻嗪药动学参数:AUC(0-t)为(107 157.31±38 056.63),(130 387.28±46 306.69)ng·mL-1·min-1;T1/2z为(108.65±20.95),(240.86±46.44)min;Tmax为(34.25±16.34),(120.00±0.00)min;Cmax为(683.44±254.03),(368.45±136.95)ng·mL-1结论 该方法准确度、精密度、回收率和基质效应均符合生物基质样品测试要求,适用于珍菊降压片在大鼠体内的药动学研究。  相似文献   

11.
New 2,6-piperidinediones 2a–g and 4a–d were prepared by initial condensation of aromatic aldehydes or cycloalkanones with cyanoacetamide to give α-cyanocinnamides la–g or cycloalkylidenes 3a,b which underwent Michae1 addition with ethyl cyanoacetate or diethylmalonate. Compounds 4a–d were alkylated by various alkyl halides to produce the N-alkylated 2,6-piperidinedione derivatives 5a–m. Some new selected compounds 2a–c,f, 4a–d & 5e,h,j were pharmacologically evaluated for potential anticonvulsant, sedative and analgesic activities. These compounds exhibited significant anticonvulsant and analgesic effects after a single I.P. administration 100 mg/kg b.wt. . On the other hand all the investigated compounds induced hypnotic activity and prolonged the phenobarbital sodium- induced sleep as compared with the control group and the most potent compound was found to be 2f.  相似文献   

12.
Policosanol is a cholesterol-lowering drug with hypocholesterolemic effects demonstrated in experimental models, healthy volunteers and type II hypercholesterolemic patients. In addition, antiplatelet effects of policosanol have been shown in experimental models and healthy volunteers. The effect of successively increasing doses of policosanol on platelet aggregation was investigated in a randomized, placebo-controlled, double-blind study conducted in 37 healthy volunteers. The volunteers were on a placebo-baseline period (two tablets per day) for 7 days and thereafter they received randomly, under double-blind conditions, placebo or policosanol (10mgday−1) for 7 days. After this period dosage was doubled to 20mgday−1for the next 7 days and then again doubled to 40mgday−1, while the control group received placebo tablets all the time. Platelet aggregation as well as coagulation time was measured at baseline and after each dosing step. Results showed that antiplatelet effects of policosanol were successfully enhanced throughout the study, thus suggesting a dose-dependent relationship. No significant effect was reached during the first dosing period, but significant reductions of epinephrine and ADP-induced platelet aggregation were observed after the second one. Finally, a significant inhibition of platelet aggregation induced by all the agonists was observed at the last dosing step. Coagulation time remained unchanged during the trial.  相似文献   

13.
目的 建立鼻渊净胶囊的高效液相色谱(HPLC)指纹图谱.方法 采用Agilent SB-C18(4.6 mm×250 mm,5μm)色谱柱,乙腈-水为流动相、以1.0 ml/min流速行梯度洗脱,检测波长210 nm,柱温30℃,洗脱时间为80 min.采用中药色谱指纹图谱相似度评价系统(2004A版)对检测出色谱进行...  相似文献   

14.
Neuramide (NMD), a substance found in crude preparations of porcine stomach extract, is a viral inhibitor that also has putative immunostimulatory effects. The effects of NMD on stress-hormone (ACTH and prolactin—PRL) release were assessed inin vivoandin vitrostudies. In the former, blood levels of corticosterone and PRL were measured in NMD-treated male rats.In vitroexperiments were performed to evaluate the effects of NMD and three of its fractions (obtained with high performance liquid chromatography) on ACTH and PRL release from perfused rat pituitary slices. NMD increased plasma corticosterone levelsin vivoand produced dose-dependent increases inin vitropituitary release of ACTH. No effects on PRL secretion were observedin vivoorin vitro. The stimulatory effects on ACTH release were caused by the NMD fraction with a molecular weight of >5000<10000Da.  相似文献   

15.
In this study, the antibiotic susceptibilities to tigecycline and tetracycline of 35 selected Bacteroides fragilis group strains were determined by Etest, and the presence of tetQ, tetX, tetX1 and ermF genes was investigated by polymerase chain reaction (PCR). tetQ was detected in all 12 B. fragilis group isolates (100%) exhibiting elevated tigecycline minimum inhibitory concentrations (MICs) (≥8 μg/mL) as well as the 8 strains (100%) with a tigecycline MIC of 4 μg/mL, whilst tetX and tetX1 were present in 15% and 75% of these strains, respectively. All of these strains were fully resistant to tetracycline (MIC ≥ 16 μg/mL). On the other hand, amongst the group of strains with tigecycline MICs < 4 μg/mL (15 isolates), tetQ, tetX and tetX1 were found less frequently (73.3%, 13.3% and 46.7%, respectively). All but two strains harbouring the tetQ gene in this group were non-susceptible to tetracycline, with a MIC > 4 μg/mL. These data suggest that in most cases tigecycline overcomes the tetracycline resistance mechanisms frequently observed in Bacteroides strains. However, the presence of tetX and tetX1 genes in some of the strains exhibiting elevated MICs for tigecycline draws attention to the possible development and spread of resistance to this antibiotic agent amongst Bacteroides strains. The common occurrence of ermF, tetX, tetX1 and tetQ genes together predicted the presence of the CTnDOT-like Bacteroides conjugative transposon in this collection of Bacteroides strains.  相似文献   

16.
Inhibitory effects of the class III antiarrhythmic compound / -sotalol on acetylcholinesterase (AChE; EC 3.1.1.7) isoenzymes of both erythrocytes and the human caudate nucleus and on serum cholinesterase (ChE; EC 3.1.1.8) were studiedin vitrousing a spectrophotometric kinetic assay with acetylthiocholine (ASCh) as substrate. Sotalol concentrations in the assays varied from 0.32 to 3.2m . All isoenzymes studied were inhibited by / -sotalol in a reversible and concentration-dependent manner. Double reciprocal plots of the reaction velocity against varying ASCh concentrations revealed that / -sotalol reduced substrate affinity (apparent Michaelis constant, KM, increased) of serum ChE, but did not change the enzyme's maximal rate of ASCh hydrolysis (Vmax). Thus, / -sotalol inhibition of serum ChE was of the competitive type (rate constant for reversible competitive inhibition: Ki=0.51m ). In contrast, / sotalol reduced the maximal reaction velocity of the AChE isoenzyme from the central nervous system (caudate nucleus), but had no influence on substrate affinity of the enzyme (KMwith ASCh unchanged) indicating purely non-competitive inhibition kinetics (rate constant of reversible non-competitive inhibition: Ki′=0.44m ). / -sotalol inhibition of erythrocyte AChE was of mixed competitive/non-competitive type (Ki=0.31m , Ki′=0.49m ). Non-competitive / -sotalol inhibition of caudate nucleus AChE and the non-competitive component of erythrocyte AChE inhibition cannot be overcome by increased concentrations of the cholinergic transmitter acetylcholine (ACh). Peak / -sotalol plasma levels as described in the literature for both humans (15μ ) and experimental animals (dogs: 18μ ; rats: 260μ ) as well as maximal myocardial concentrations of the substance (dogs: 46μ ; rats: 478μ ) are in the range of about 2% to 100% of the sotalol inhibition rate constants determined in the present paper for cholinesterase isoenzymesin vitro. Thus, / -sotalol inhibition of ACh hydrolysisin vivomay contribute to both the well known antiarrhythmic potential and proarrhythmic side effects of the compound.  相似文献   

17.
Cyclosporine A, beside its current applications, possesses potential hepatoprotective effects. This study was directed to investigate the effect of Cyclosporine A pretreatment on hepatic injury due to carbon tetrachloride (CCl4) and -galactosamine. Rats were injected by two successive doses of Cyclosporine A (5mgkg−1day−1). Six hours after the second dose, 1mlkg−1of CCl4was administered i.p. Effects associated with Cyclosporine A pretreatment were examined by using isolated hepatocytes and hepatocytes that were immobilized and continuously perfused. -Galactosamine (5m ) was added directly to the perfusion medium. After isolation, hepatocytes were examined histologically by light and electron microscopy, immobilized and perfused for further metabolic functional activity evaluation. Cyclosporine A pretreatmentin vivoproduced hepatoameliorative effects of various degrees which were statistically significant as manifested by: (1) an increased trypan blue exclusion after CCl4; (2) an improved ureagenesis after CCl4; (3) a reduction in the lipid droplets accumulation in the cytoplasm produced by CCl4administration; (4) well preserved cytoplasmic organelles as mitochondria, endoplasmic reticulum ER, nuclear chromatin structures that were altered by CCl4; and (5) an increased hepatocytes survival in the agarose gel matrix, reduction of LD leakage and improvement of ureagenesis after -galactosamine addition to the perfusion medium. The beneficial effect of Cyclosporine A pretreatment in modifying hepatotoxicity of chemical insults merits further studies.  相似文献   

18.
喙果黑面神化学成分研究   总被引:2,自引:0,他引:2  
目的研究大戟科植物喙果黑面神(Breynia rostrata Merr.)的化学成分。方法利用硅胶、凝胶等色谱技术分离纯化化学成分,根据化合物的理化性质和光谱数据进行结构鉴定。结果从喙果黑面神的正丁醇萃取部分分离得到4个化合物,分别鉴定为6-O-甲基丙酰基-α-D-吡喃葡糖(6-O-methylpropanoyl-α-D-glucopyranose,1);4″-苯酚基-6-O-甲基丙酰基-β-D-吡喃葡糖苷(4″-phenolic-6-O-methylpropanoyl-β-D-glucopyranoside,2);1-O-没食子酰基-β-D-吡喃葡糖苷(1-O-galloyl-β-D-glucopyranoside,3);熊果苷(arbutin,4)。结论化合物1和2为新化合物,3和4均为首次从该种植物分离得到。  相似文献   

19.
In this study 2-guanidine-4-methylquinazoline (2-GMQ) appeared to decrease basal and stimulated gastric acid secretion, while structurally related compounds as dimethyl- biguanide, cyanoguanidine and 2-cyanoamino-4-methylpyrymidine did not. Thus, there is an antisecretory effect when the biguanide group is associated with a lipophilic structure. The antisecretive effects exerted by 2-GMQ are associated with anti H2-histamine activity.The anti H2-histamine nature of the effects of 2-GMQ was confirmed by the capacity of this compound of depressing the chronotropic activity of the isolated guinea pig auricle increased by histamine, as well as relaxant activity in rat uterus contracted by histamine, since both preparations are rich in H2-histamine receptors.  相似文献   

20.
穆向荣  林林  焦阳  林永强 《药学研究》2019,38(7):419-423
瓜蒌子、瓜蒌皮、瓜蒌、天花粉来源于栝楼的不同药用部位,4味药材均为常用的大宗药材,现行版《中国药典》对其制定的质量标准过于简单,无法科学合理地控制其质量。本文对瓜蒌子、瓜蒌皮、瓜蒌、天花粉安全性和有效组分的研究进行综述,明确了相关研究存在的问题并针对问题提出建议,为科学全面的药材及饮片标准的制定提供参考依据。  相似文献   

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