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.     

T1Effects in Sequential Dynamic Susceptibility Contrast Experiments

Residual effects of an initial bolus of gadolinium contrast agent have been previously demonstrated in sequential dynamic susceptibility contrast MR experiments. While these residual effects quickly reach a saturation steady state, their etiology is uncertain, and they can lead to spurious estimates of hemodynamic parameters in activation experiments. The possible influence ofT₁effects is now investigated with experiments in whichT₁weighting is varied as well as with serial regionalT₁measurements. Little evidence for significant residualT₁effects is found, suggesting instead that susceptibility effects underlie these observations. An initial saturation dose of contrast agent minimizes this effect.     

Endoscopic Observation of Tissue by Narrowband Illumination

We propose a new illumination method for a medical endoscope: narrow band imaging (NBI), in which the spectral bandwidth of the filtered light is narrowed. To confirm how the spectral specifications of the filtered light influence a reproduced image, an experiment was conducted observing the endoscopic images of the back mucosa of a human tongue. In addition, the effect of NBI on endoscopic images was investigated through preliminary clinical tests in colonoscopy and upper gastrointestinal endoscopy. It has been shown that NBI can enhance the capillary pattern and the crypt pattern on the mucosa. These patterns are useful features for diagnosing an early cancer.     

原子吸收法测定血清中的无机磷和钙

本文叙述了用原子吸收法测定同一个少量血清样品中的无机磷和钙。血清用高氨酸沉淀蛋白后,加过量钼酸铵。在pH0.4～1.6范围内,用乙酸丁酯萃取生成的微量磷钼酸,与过量的钼酸铵分离。水相测钙,有机相用稀氨水反萃后测钼,间接分析磷。     

降铅冲剂对低水平铅暴露仔鼠血铅及脑铅的影响

目的:研究降铅冲剂对低水平铅暴露仔鼠血铅及脑铅的影响,为评价降铅冲剂的作用提供依据。方法:选用Wister大鼠仔鼠60只,体质量80~100 g,随机分成6组,每组10只,分别为空白组、模型对照组、EDTA对照组、降铅冲剂低剂量组、降铅冲剂中剂量组、降铅冲剂高剂量组;造模后开始给药,EDTA对照组给CaNa2EDTA注射液10(mg/kg)/d腹腔注射,降铅冲剂低、中、高剂量组分别予降铅冲剂5(g/kg)/d、10(g/kg)/d、20(g/kg)/d的剂量灌胃,空白组和模型对照组予等量蒸馏水灌胃,给药共30 d。用石墨炉原子吸收光谱仪测定仔鼠血铅、脑铅。结果:(1)染铅后,各染铅组的血铅水平与空白组比较都显著升高(P<0.001),经过30 d的治疗后,各治疗组的治疗后血铅水平均有不同程度下降,与模型对照组比较均有统计学意义。(2)染铅后,各染铅组的脑铅水平与空白组比较都显著升高(P<0.05),治疗后,各组脑铅与治疗前比较均显著升高,降铅冲剂低、中剂量组的脑铅与模型对照组比较显著下降。结论:降铅冲剂能显著降低低水平铅暴露仔鼠的血铅和脑铅含量,其综合疗效优于CaNa2EDTA。     

红珍珠降糖胶囊中微量元素营养研究

红珍珠降糖胶囊是具有显著降低血糖水平,确定糖尿病患者康复的绿色营养保健食品。通过红珍珠降糖胶囊中Cr、Mn、Cu、Zn、Mg等微量元素的分析测试以及与青海小麦、膳食日摄取量等对比研究,表明红珍珠降糖胶囊富含涉及糖尿病的微量元素,在降低血粮糖水平方面具有十分重要的营养学、功效学作用和意义。     

人血中10种常见毒品的GC-MS同时检测方法研究

建立了同时检测人血液中鸦片类、巴比妥类和苯二氮卓类10种常见毒品的气相色谱-质谱新方法。系统地对提取溶剂及其组成配比、体系pH值、超声振荡提取时间等样品预处理条件以及色谱柱等GC-MS分析条件进行考察和优化。运用选择离子模式(SIM)检测,每种成分选择4个特征离子。所选的离子分别为:摇头丸m/z44、77、136、207;异戊巴比妥m/z156、55、141、41;司可巴比妥m/z168、97、195、41;咖啡因m/z194、82、109、67;安眠酮m/z235、213、250、91;美沙酮m/z72、57、165、213;吗啡m/z271、150、201、81;安定m/z256、221、283、165;氯氮平m/z243、227、256、192;艾司唑仑m/z207、239、293、259,其中黑斜体为定量离子。在选定的条件下,异戊巴比妥等7种药物在0.10~25.0 mg/L范围内线性关系良好,安定等3种药物在0.50~25.0 mg/L范围内线性关系良好,方法回收率在96%~103%之间,RSD在1.64%~6.32%之间,检出限为0.01~0.05 mg/kg。本文同时研究了pH值对吗啡类药物的影响机理。与文献报道的检测方法比较,本法更加简便易行,灵敏度提高1个数量级以上,分析时间缩短,用色谱保留时间与质谱同时定性,消除血液中其他成分干扰,结果准确可靠,选择性和重复性好,可应用于中毒患者体液样品及毒物成分的分析检测。     

An improved enzymatic assay for glucose determination in blood serum using a l,1′-dimethylferricinium dye

l,l′-dimethylferricinium (DMFe⁺),a stable and pH-insensitive blue dye, was prepared via enzymatic oxidation of a 1,1′-dimethylferrocene (DMFe):2-hydroxypropyl-β-cyclodextrin (HPCD) watersoluble inclusion complex, using bilirubin oxidase immobilized onto porous aminopropyl glass beads via glutaraldehyde activation. In the presence of glucose, DMFe⁺ was reduced to DMFe by reacting with the reduced glucose oxidase (FADH₂), and the absorbance decrease was followed at 650 nm. In acetate pH 5.2 buffer, the response to glucose in blood serum was nonlinear, especially in the low concentration range, because of a competition for the reduced glucose oxidase between the DMFe⁺ dye and oxygen. At this pH, endogenous ceruloplasmin was also observed to oxidize residual DMFe (16%) in the dye preparation, causing an increase in absorbance at 650 nm. An assay protocol was then developed using maleate buffer, pH 6.5, to overcome these interferences as well as mutarotation of α-D-glucose. The results obtained for glucose in the blood serum samples agreed well with those of the reference hexokinase/glucose-6-phosphate dehydrogenase method.     

纳米CoHCF修饰电极的制备及其对血红蛋白的电化学测定研究

A cobalt hexacyanoferrate （CoHCF） nanoparticle （size ca. 60 nm） chemically modified electrode （CME） was fabricated and the electrochemical behavior of hemoglobin （Hb） at this nanosized CoHCF CME was studied. In comparison with a bare glassy carbon electrode （GCE） and a general CoHCF CME electrodeposited in a traditional manner, the present nanosized CoHCF CME performed efficiently electrocatalytic reduction for Hb with relatively high sensitivity, stability, and longlife, Combined with liquid chromatography （LC）, the nanosized CoHCF CME was used as the electrochemical detector of Hb in the established flow injection analysis-electrochemical determination （FIA-ECD） system. The peak current was a linear function of concentrations in the range from 2.5×10^-8 to 5.0×10^-6mol/L for Hb, with detection limit of 1.4×10^-8 mol/L. The FIA-ECD system has been successfully applied to assess the Hb content of clinic blood samples with advantages of sensitiveness, speediness, easy control and small sample-consumption.