A dried blood spot assay with HPLC–MS/MS for the determination of larotrectinib in mouse blood and its application to a pharmacokinetic study

Larotrectinib is a first-generation tropomyosin kinase inhibitor, approved for the treatment of solid tumors. In this paper, we present a validated dried blood spot (DBS) method for the quantitation of larotrectinib from mouse blood using HPLC–MS/MS, which was operated under multiple reaction monitoring mode. To the DBS disc cards, acidified methanol enriched with internal standard (IS; enasidenib) was added and extracted using tert-butyl methyl ether as an extraction solvent with sonication. Chromatographic separation of larotrectinib and the IS was achieved on an Atlantis dC₁₈ column using 10 mm ammonium formate–acetonitrile (30:70, v/v) delivered at a flow-rate of 0.80 ml/min. Under these optimized conditions, the retention times of larotrectinib and the IS were ~0.93 and 1.37 min, respectively. The total run time was 2.50 min. Larotrectinib and the IS were analyzed using positive ion scan mode and parent–daughter mass to charge ion (m/z) transitions of 429.1 → 342.1 and 474.1 → 267.1, respectively, were used for the quantitation. The calibration range was 1.06–5,080 ng/ml. No matrix effect or carryover was observed. Hematocrit did not influence DBS larotrectinib concentrations. All of the validation parameters met the acceptance criteria. The applicability of the validated method was shown in a mouse pharmacokinetic study.     

用VC++.NET编写鼠标交互式绘图程序

主要介绍了在面向对象的VC .NET语言环境下,通过使用WM_LBUTTONDOWN, WM_MOUSEMOVE, WM_LBUTTONUP等鼠标事件消息,采用橡皮条绘图法,编写一个鼠标交互式绘图程序.该程序可实现绘制随机的平面图形,也可通过鼠标的拖动画出大小不同的圆,椭圆,矩形,直线等平面图形.     

A Study of Protein and Glycoprotein Syntheses in Pre-implantation Mouse Embryos Using Mini-2D-Electrophoresis, Video Densitometer Scanning and Computer-Image Analysis

In the present study, proteins and glycoproteins of mouse embryos at 2-cell,morula and blastocyst stages were analyzed.The techniques of ~(35)S-Met incorporation,ConA antiserum-precipitating ConA-binding proteins, mini-2D-electrophoresis, fluorography,video densitometer scanning and the computer-lmage system were used for analyses.Results of the investigations indicated that proteins and glycoproteins were synthesized by the embryos in a gradual increase manner from 2-cell to blastocyst. A relatively large amount of glycoproteins was synthesized during the morula and blastocyst stages.Two specific small glycoproteins respectively with molecular weights about 6500 and 9000 and PIs at 5.0 and 6.5 were apparently synthesized in the blastocyst but not in the 2-cell or the morula.     

乙醇对小白鼠胚胎的毒性和维生素的解毒作用

乙醇对小白鼠有致畸效应,尤其是对中枢神经系统(CNS)和骨骼系统.适量的维生素B_1和烟酰胺能解除由乙醇引起的小白鼠胎鼠毒害作用.     

兔子和小鼠不同组织苹果酸脱氢酶活性的研究

本文采用苹果酸脱氢酶(M DH)催化过程中辅酶Ⅰ氧化还原型转化的特征,测定了兔子和小鼠不同组织M DH的比活力和米氏常数(km),比活力在370~1 055单位/m g蛋白之间,km范围为3.57~6.49×1-0 5m o l/L.快速老化小鼠病理模型的km增大10倍,为1.49~5.64×10-4m o l/L.     

浅析农田鼠害回升原因及防治策略

分析了农田鼠害回升的主要原因,在此基础上提出了相应的防治策略,包括提高思想认识,加强鼠情动态监测,开展综合防治等。     

小鼠腹水癌细胞脂酶的亲和制备及一些性质的研究

在接种了血癌(L—7712)及腹水癌(Hep.A)的小鼠腹水癌细胞中存在远高于正常细胞的脂酶(Lipase)活力.本文通过免疫亲和层析方法从小鼠腹水癌细胞中纯化了该脂酶,比活力达到2000国际单位/mg.蛋白.经 SDS 聚丙烯酰胺凝胶电泳分析,纯度达电泳纯,为单亚基酶.分子量65kd.经等电聚焦电冰分析,等电点(PI)为5.3.     

野生和人工养殖暗纹东方鲀不同组织中河豚毒素(TTX)含量的初步研究

采用小鼠生物检测法测定了野生和人工养殖暗纹东方不同组织中河豚毒素（ＴＴＸ）的含量．野生暗纹东方不同组织中ＴＴＸ含量由高到低依次是：卵巢、肝脏、胃肠、肾脏,肌肉毒性最小;而人工养殖暗纹东方不同组织中ＴＴＸ含量都极低,几乎无毒．结果表明,用人工养殖方法可以培育出低毒或无毒河豚,在一定程度上支持了河豚毒素的微生物起源学说．     

褪黑素对持续光照小鼠学习记忆能力的影响

运用Ｙ－迷宫检测小鼠的分辨学习和记忆能力,观察了年龄,每天２４小时连续１个月的持续光照和每日定时注射褪黑素对小鼠分辨学习和记忆能力的影响。结果表明,成年小鼠与青年小鼠相经学习和记忆能力下降;持续光照可引起小鼠学习记忆能力出现不同程度的下降;实验结果提示,褪黑素在维持学习记忆能力中具有重要作用。     

无毛小鼠繁育及其特性的初步观察

在KM小鼠饲养过程中发现并培育了 19代无毛小鼠 ,该小鼠在二级环境条件下能存活 2 4个月左右 ,可能是一个新的突变系 ,因此 ,我们对该无毛小鼠的生物学特性进行了初步的观察。我们在KM小鼠饲养中发现同窝小鼠中有无毛小鼠雌雄各一只 ,后将其有意保留下来 ,对其后代采取同胞兄妹随机交配的方式进行繁殖 ,目前已经繁殖到 18— 19代。在传至 7— 9代时出现繁殖力下降的现象 ,采取堂兄妹交配的方式后逐渐恢复正常繁殖。通过观察和实验证明 ,该小鼠的脱毛现象与年龄老化、营养、环境和寄生虫感染无关 ,脱毛形状也无性别特点 ,母鼠有能力哺乳小…