高效液相色谱法测定乙烷硒啉注射剂中乙烷硒啉的含量(英文)

采用高效液相色谱法测定乙烷硒啉注射剂中乙烷硒啉的含量。使用ODS色谱柱, 流动相组成0.01%磷酸-甲醇 (60:40, v/v), 流速1.0 mL/min, 柱温40 °C, 检测波长320 nm, 进样体积20 μL。结果表明: 在上述色谱条件下乙烷硒啉色谱峰峰型良好, 在10-50 μg/mL浓度范围内, 乙烷硒啉浓度与峰面积之间线性良好 (r2 = 0.9999), 最低检测限为100 ng/mL, 精密度、日间与日内差、稳定性、回收率均符合要求。自制三批乙烷硒啉注射剂的含量以标示量计, 在102%-103%之间。本法简单、准确、可靠, 可用于乙烷硒啉注射剂含量的测定。     

乙烷硒啉分散片溶出度测定方法的研究*

目的:建立乙烷硒啉分散片的溶出度测定方法。方法:建立溶出度紫外测定方法,分别考察乙烷硒啉分散片在不同条件下的溶出特性,运用Excel办公软件,以Weibull模型处理试验数据,用单因素方差分析及t检验进行统计学分析。结果:在优化的测定条件下,乙烷硒啉分散片60min累积溶出度达到(65.59±0.36)%,批内均一性与批间重现性良好。结论:本品溶出度优化测定条件为:溶出介质量为1000mL,溶出介质组成为0.9%盐酸水溶液-异丙醇(60∶40),采用药典附录ⅩC第二法(桨法),转速为150r.min-1。取样点为60min,限度为60%。     

紫杉醇脂质体在大鼠和荷瘤裸鼠体内的组织分布

目的：运用LC—MS／MS法测定紫杉醇脂质体在大鼠和荷瘤裸鼠体内的组织分布,比较注射用紫杉醇脂质体和紫杉醇注射液的体内分布特征。方法：大鼠分组后分别iv．7mg·kg-1受试和参比试剂,于给药前、给药后10min、1h、4h采集组织样品;荷瘤裸鼠分组后分别iv．10mg·kg-1受试和参比试剂,于给药前、给药后10min,1h,4h,8h采集组织样品,利用LC—Ms／Ms法对组织样品中药物含量进行测定。结果：大鼠iv．紫杉醇脂质体后10min在肝、心、肾、脑、子宫分布达到最大值．4h后各组织中药物含量均下降：荷瘤裸鼠iv．给药后10min在血、肝、脾、肺、肾、脂肪、睾丸分布量最大,8h后在脾、肠、肝、肿瘤中药物含量依然较高。结论：紫杉醇脂质体和紫杉醇注射液在大鼠和裸鼠体内的组织分布一致。静脉注射紫杉醇脂质体后．均能特异地分布到肝脏、肺和肠等。两制剂比较,紫杉醇脂质体具有更好的靶向性和更高的安全性。     

RP-HPLC法测定乙烷硒啉分散片中药物的含量*

目的:建立乙烷硒啉分散片含量测定方法。方法:采用反相高效液相色谱法,使用BDS HYPERSILC18柱(250mm×4.6mm,5μm),检测波长为320nm,柱温为室温,流动相为0.01%磷酸-甲醇(60∶40),流速1.0mL.min-1。结果:溶剂与辅料对分散片中药物的含量测定无干扰,乙烷硒啉在10～400μg.mL-1范围内呈良好的线性关系(r=0.9995),精密度RSD为0.39%;日内精密度为0.57%;平均回收率为101.2%(n=9)。结论:该方法专属性强,操作方便,结果准确,重现性好,可用于乙烷硒啉分散片中药物的含量测定。     

乙烷硒啉对H-22荷瘤鼠CYP450酶系影响

[摘要]目的：观察新药乙烷硒啉（BBSKE）对肿瘤H-22引起的小鼠肝脏细胞色素P450含量及其主要亚型活性变化的影响。方法：H-22荷瘤小鼠,给予不同剂量的BBSKE 10d后,提取肝微粒体,Omura法测定CYP450的含量,分光光度法测定CYP1A,CYP3A和CYP2E1活性。结果：肿瘤H-22能引起CYP1A活性升高（P＜0.01）,CYP3A活性降低（P＜0.01）;BBSKE能明显下调荷瘤鼠CYP1A活性,上调CYP3A活性作用（P＜0.05）。肿瘤H-22和BBSKE对CYP450含量和CYP2E1均无明显影响。结论：BBSKE对荷瘤鼠CYP1A活性有下调作用;对CYP3A有诱导作用;对CYP2E1无明显影响。     

活性氧族介导乙烷硒啉在A549细胞中诱导的快速凋亡

硫氧还蛋白还原酶（TrxR）是哺乳动物细胞内负责清除过量活性氧族（ROS）的重要酶类。本研究的目的是探究ROS在TrxR抑制剂乙烷硒啉抗肿瘤机制中的作用。在人肺癌细胞A549中,乙烷硒啉迅速诱导ROS含量上升和线粒体膜电位下降,并导致细胞死亡。ROS清除剂N-乙酰半胱氨酸的预孵育可以显著抵抗这三种现象。AnnexinV-PI法和Western blot的结果表明乙烷硒啉激活了内源性凋亡通路。线粒体通透性转变孔道抑制剂环孢菌素A可以抑制乙烷硒啉诱发的细胞色素c释放和细胞死亡,而同时一些Bcl-2家族蛋白含量却没有明显变化。这些结果说明ROS可能部分地通过增加线粒体通透性,释放包括线粒体内的促凋亡因子来介导乙烷硒啉诱发的快速凋亡。首次报道了ROS可能在乙烷硒啉抗肿瘤机制,特别是其早期过程中有重要作用。     

乙烷硒啉的临床药物动力学和代谢转化特点研究

目的研究肿瘤患者口服乙烷硒啉(1,2-[bis(1,2Benzisoselenazolone-3(2H)-ketone)]ethane,BBSKE)后的药物动力学及体内代谢转化特征。方法3例肿瘤患者单次口服给药剂量为600mg.d-1,采集各个时间点的血浆样品及尿样,用液相色谱-串联四极杆质谱(LC/ESI-MS/MS)联用技术测定血浆样品中BBSKE的含量,用液相色谱-电喷雾离子阱质谱(LC-ESI/MSn)联用技术对尿及血浆中的代谢产物进行分析鉴定。结果得到了BBSKE在血浆中的药时曲线图及主要的药物动力学参数。在尿中共发现了6个BBSKE的氧化、甲基化、葡萄糖醛酸化代谢产物,在血浆中共发现了2个BBSKE的氧化、葡萄糖醛酸化代谢产物。结论BBSKE的血药浓度较低,表观分布容积大。氧化、甲基化、葡萄糖醛酸化反应是BBSKE在人体内的3种重要代谢途径。     

液相色谱-串联质谱法分析抗肿瘤新药乙烷硒啉在大鼠体内的代谢产物

本研究对抗肿瘤新药1,2-[二(1,2-苯并异硒唑-3(2H)-酮)]乙烷(乙烷硒啉,BBSKE)在大鼠体内的代谢产物进行鉴定。在灌胃给予大鼠单剂量乙烷硒啉200mg·kg-1后,采用液相色谱-串联质谱法(LC-MSn)对大鼠尿液、粪样、胆汁和血浆中的代谢产物进行检测,通过全扫描和选择离子扫描,以及根据多级质谱裂解规律对代谢物的结构进行分析。研究发现在大鼠尿样、粪样、胆汁和血浆中检测到3种Ⅰ相代谢产物和1种Ⅱ相代谢产物,其代谢途径分别为氧化、甲基化、硫甲基化和葡萄糖醛酸化反应,提示乙烷硒啉在大鼠体内的代谢方式可能是通过氧化、甲基化及葡萄糖醛酸化反应形成代谢产物。     

荷瘤小鼠体内光敏胶束制剂的分布研究

目的：考察C₆₀/Fe₃O₄-UCNPs@DTX@SNSC在荷瘤小鼠体内的分布特征。方法：采用高效液相色谱法,记录色谱图,计算C₆₀/Fe₃O₄-UCNPs@DTX@SNSC在体内的血药浓度和组织浓度。结果：C₆₀/Fe₃O₄-UCNPs@DTX@SNSC在肿瘤组织中的药物浓度相对较大。结论：制备的C₆₀/Fe₃O₄-UCNPs@DTX@SNSC能够能够显著延长药物在体内的半衰期,增强其抗肿瘤效果。     

铼与抗结肠癌单克隆抗体的直接标记法及在荷瘤裸鼠体内的放射免疫显像

为探讨^180铼(^186Re)用于放射免疫显像的价值．用抗入结肠癌单克隆抗体(MAb)SC3A和以抗坏血酸为还原荆的直接标记法．对SnCl2还原的180RE标记物在荷结肠癌裸鼠体内的生物学分布及放射免疫显像进行研究。结果显示．本法的标记率均达96%～99%标记物较稳定．在体与250倍以上的二乙烯三胺五乙酸(DTPA)和人血清白蛋白在37℃共育24h．未见标记物786Re-SC3A解离。用过量肿瘤细胞抗原结合法测定．标记物抗体活性达90%～96％，48h活性下降相似文献   

Comparative tissue distribution and excretion of orally administered [3H]diacetoxyscirpenol (anguidine) in rats and mice

A quantitative comparison of tissue distribution and excretion of an orally administered sublethal dose of [3H]diacetoxyscirpenol (anguidine) was made in rats and mice 90 min, 24 hr, and 7 days after treatment. Total recoveries of 95-100% were obtained. Approximately 90% of the dose was excreted in urine and feces during the first 24 hr with a feces:urine ratio of about 1:4.5 in both species. Carcass and tissue radioactivity dropped rapidly during the first 24 hr but remained relatively constant at low, but detectable, levels (1.5-3.5% of dose) over the course of the experiment. Few substantive interspecies differences were noted in tissue distribution. At 90 min the highest percentage of dose was in tissues involved in sequestering diacetoxyscirpenol because of high body water/lipid content (carcass, skin) or the absorption (stomach, small intestine), metabolism (liver), or excretion (kidney) of the toxin. The rank order of these tissues was generally stable over the course of the experiment. When data were expressed as specific radioactivity (dpm/g tissue) instead, the carcass and skin dropped from the top rank tissues at 90 min and were replaced by the spleen and cecum. At 24 hr and 7 days the top-ranked order of tissues shifted to include organs associated with trichothecene-induced toxicity such as the lymphohematopoietic system (spleen, thymus, and femur bone marrow), heart, and testis (in mouse) as well as the cecum and large intestine. In addition, the rate of loss of radioactivity with time generally did not decrease as rapidly in these target organs as observed in liver, kidney, skin, and carcass. Brain radioactivity, though very low, also diminished relatively slowly. Significant differences in specific radioactivity which did occur between the rat and mouse tended to occur in target organs and with the higher levels present in the mouse. These data were discussed in terms of interspecies differences in lethality and target organ toxicity.     

Pharmacokinetics of 3-[bis(2-hydroxyethyl)amino]acetophenone [4,5-diphenyloxazolyl-(2)]hydrazone (ZIMET 98/69) in rats

The pharmacokinetics of 3H-ZIMET 98/69 after i.v. and oral administration to rats was studied. After i.v. administration of 2.5 and 10 mg/kg a biphasic exponential decay of total serum radioactivity was found, so that a two compartment open model could be assumed. Oral administration of 10 mg/kg results only a moderate bioavailability (25%), which further decreased after administration of higher doses. The distribution steady state between serum and tissue is reached rapidly. Elimination proceeds slowly, the serum half-life being 64-84 h.     

Pharmacokinetics and tissue distribution of the new non-imidazole histamine H3 receptor antagonist 1-[3-(4-tert-butylphenoxy) propyl]piperidine in rats

Abstract

1.?The aim of this study was to evaluate pharmacokinetics and tissue distribution of novel histamine H3 receptor antagonist 1-[3-(4-tert-butylphenoxy)propyl]piperidine (compound DL76).

2.?Following intravenous administration of DL76 at the dose of 3?mg/kg, pharmacokinetic parameters were calculated using non-compartmental analysis. The systemic serum clearance was 10.08?L/h/kg and the estimated blood clearance was 5.64?L/h/kg. The volume of distribution at steady state was 16.1?L/kg which was greater than total body water, terminal half-life and MRT equalled 1.41?h and 1.6?h, respectively. The two-compartment pharmacokinetic model with enterohepatic circulation was also successfully fitted to the experimental data.

3.?After systemic administration, DL76 was rapidly distributed into all organs studied (liver, kidney, brain, and lung). The highest AUC of DL76 was observed in lungs followed by brain, where the exposure to the investigated compound expressed as AUC was almost 30 times higher than in serum.

4.?Bioavailability, calculated based on the area-under-the-concentration–time curve extrapolated to infinity after intravenous and intragastric administration of the dose 3?mg/kg, equalled 60.9%.     

The pharmacokinetics of [3H]1-[1-(2-thienyl)cyclohexyl]piperidine (TCP) in Sprague-Dawley rats

Using adult male Sprague-Dawley rats, we examined the blood protein binding and pharmacokinetics of the potent phencyclidine (PCP) receptor ligand 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP). The average percentage of unbound [3H]TCP in rat serum was 42 +/- 6% and the [3H]TCP blood to plasma ratio was 0.98 +/- 0.03 (mean +/- SD, n = 5 in both studies). For the pharmacokinetic studies, [3H]TCP and 1 mg/kg unlabeled TCP were administered as an iv bolus dose. The average [3H]TCP elimination half-life was 2.1 hr. In contrast, total radioactivity in the plasma had a much longer half-life, suggesting much slower metabolite elimination. The average distribution volumes were 27 +/- 17, 15.6 +/- 6.2, and 5.6 +/- 3.0 liters/kg for V beta, Vss, and Vc, respectively. Total body and renal clearance values were 132 +/- 45 and 1.1 +/- 0.4 ml/min/kg, respectively. When TCP pharmacokinetic parameters were compared to PCP pharmacokinetic data in rats from a previous study, a strikingly similar pharmacokinetic profile was found. These data indicated that TCP and PCP are equivalent, from a pharmacokinetic point of view, and that the higher pharmacological potency of TCP over PCP is probably due to receptor-mediated differences.     

Teratological study of 4-ethoxy-2-methyl 5-morpholino-3(2H)-pyridazinone (M73101) in mice and rats (author's transl)]

M73101 was given orally to pregnant mice (0, 100, 400 and 800 mg/kg/day) and rats (0, 100, 300 and 600mg/kg/day) during the major organogenesis to assess the influences of prenatal and postnatal development of progeny. There were no apparent effects of M73101 on litter size, fetal mortality or sex ratio in both species, although slight decrease in body weight occurred in fetuses of mice and rats exposed to the largest dose. No external, internal or skeletal malformations attributable to M73101 were observed in mouse and rat fetuses. No apparent influences of M73101 on postnatal development of mouse or rat offspring were seen.