Determination of zolmitriptan in human plasma by liquid chromatography-tandem mass spectrometry method: application to a pharmacokinetic study

A sensitive and selective liquid chromatography-tandem spectrometry method for the determination of zolmitriptan was developed and validated over the linearity range 0.05-30 ng/ml with 0.5 ml of plasma using diphenhydramine as the internal standard. Liquid-liquid extraction using a mixture of diethyl ether and dichloromethane was used to extract the drug and the internal standard from plasma. The mass spectrometer was operated under the selected reaction monitoring (SRM) mode using the atmospheric pressure chemical ionization (APCI) technique. The instrument parameters were optimized to obtain 3.0 min run time. The mobile phase consisted of acetonitrile-water-formic acid (70:30:0.5), at a flow rate of 0.5 ml/min. In positive mode, zolmitriptan produced a protonated precursor ion at m/z 288 and a corresponding product ion at m/z 58. And internal standard produced a protonated precursor ion at m/z 256 and a corresponding product ion at m/z 167. The inter- and intra-day precision (%R.S.D.) were less than 8.5% and accuracy (%error) was less than -2.5%. The method had a lower limit of quantification of 0.05 ng/ml for zolmitriptan, which offered increased sensitivity and selectivity of analysis, compared with existing methods. The method was successfully applied to a pharmacokinetic study of zolmitriptan after an oral administration of 5 mg zolmitriptan to 20 healthy volunteers.     

我多组学关联分析揭示表观等位基因在拟南芥环境适应性进化中的作用及机制

表观等位基因一般是指仅由DNA甲基化差异引起的表达量不同的等位基因,对植物形态结构和各种生理过程具有重要影响。但自然条件下环境因素对植物表观等位基因的影响还不清楚,同时表观等位基因在植物环境适应性进化中的作用和机制还亟待探究。为了在全基组水平鉴定拟南芥(Arabidopsis thaliana)中与特定环境因素相关的表观等位基因,并分析它们参与拟南芥环境适应性进化的可能机制,本研究利用623株拟南芥生态型的转录组、甲基化组和种源地气候数据进行多组学关联分析,并同时进行了蛋白互作网络和基因富集分析。以春季和夏季降水量为例,本研究最终鉴定到5个基因(AGL36、AT2G34100、AT4G09360、LSU4和AT5G56910)可能具有相应的表观等位基因,基因内部或附近特定区域不同甲基化水平对它们的表达可能具有调控作用。其中与种子发育有关的印记基因AGL36首次被发现可能作为表观等位基因参与拟南芥环境适应性进化,其他4个基因均与生物胁迫响应有关。自然条件下降水量能影响当地病虫害的严重程度,而DNA甲基化能通过影响这4个免疫基因的表达来影响拟南芥免疫能力。在长期演化过程中有利于个体适应当地降水模式的表观等位基因受到正向选择,这可能是这些表观等位基因参与拟南芥降水适应性进化的潜在机制。通过蛋白互作网络、GO功能分析和KEGG通路分析,本研究还首次发现LSU4可能与LSU基因家族其他成员一样参与硫代谢网络,并通过影响硫代葡萄糖苷代谢参与拟南芥生物胁迫响应。     

Novel MUC1 aptamer selectively delivers cytotoxic agent to cancer cells in vitro

Chemotherapy is a primary treatment for cancer, but its efficacy is often limited by the adverse effects of cytotoxic agents. Targeted drug delivery may reduce the non-specific toxicity of chemotherapy by selectively directing anticancer drugs to tumor cells. MUC1 protein is an attractive target for tumor-specific drug delivery owning to its overexpression in most adenocarcinomas. In this study, a novel MUC1 aptamer is exploited as the targeting ligand for carrying doxorubicin (Dox) to cancer cells. We developed an 86-base DNA aptamer (MA3) that bound to a peptide epitope of MUC1 with a K(d) of 38.3 nM and minimal cross reactivity to albumin. Using A549 lung cancer and MCF-7 breast cancer cells as MUC1-expressing models, MA3 was found to preferentially bind to MUC1-positive but not MUC1-negative cells. An aptamer-doxorubicin complex (Apt-Dox) was formulated by intercalating doxorubicin into the DNA structure of MA3. Apt-Dox was found capable of carrying doxorubicin into MUC1-positive tumor cells, while significantly reducing the drug intake by MUC1-negative cells. Moreover, Apt-Dox retained the efficacy of doxorubicin against MUC1-positive tumor cells, but lowered the toxicity to MUC1-negative cells (P<0.01). The results suggest that the MUC1 aptamer may have potential utility as a targeting ligand for selective delivery of cytotoxic agent to MUC1-expressing tumors.     

Genome-Wide Identification and Expression Analysis of Thioredoxin (Trx) Genes in Seed Development of Vitis vinifera

Journal of Plant Growth Regulation - Thioredoxin (Trx) genes are ubiquitous in plants and have many regulatory functions. These include seed germination, apoptosis, and cellular redox processes. In...     

Facile synthesis of hybrid sulfonophosphinodipeptides composing of taurines and 1-aminoalkylphosphinic acids

Both sulfonopeptides and phosphonopeptides are important analogs of naturally occurring peptides and have been widely used as enzyme inhibitors and haptens for producing catalytic antibodies due to their tetrahedrally structural features. A series of hybrid sulfonophosphinodipeptides composing of taurines and 1-aminoalkylphosphinic acids were first and conveniently synthesized in satisfactory to good yields via a Mannich-type reaction of N-benzyloxycarbonylaminoalkanesulfonamides, aldehydes, and aryldichlorophosphines, and subsequent hydrolysis. The current method provides an efficient and direct synthesis of hybrid sulfonophosphinodipeptides.     

羧基化石墨烯/半胱胺修饰金电极对多巴胺的电化学行为研究

为了基于羧基化石墨烯/半胱胺修饰金电极建立更为先进的多巴胺生物传感器，以定量检测儿茶酚胺类神经递质多巴胺，利用自组装技术将半胱胺修饰于金电极上，再利用1-乙基-\[3-二甲基氨基丙基\]碳酰二亚胺盐酸化物/N-羟基琥珀酰亚胺（EDC/NHS）交联剂将羧基化石墨烯固定在修饰后的金电极上制成多巴胺电化学传感器。先对修饰电极进行表征以检验其灵敏度，再利用循环伏安法研究该电极在多巴胺溶液中的电化学行为，包括检测条件的优化和传感器性能的测定。修饰电极表征结果表明，羧基化石墨烯/半胱胺修饰金电极提高了电极传递电子的能力，具有较高的灵敏度。经单因素实验得出，最佳检测条件为利用pH 6.00的0.30 mol·L-1磷酸盐缓冲溶液（PBS）配制多巴胺溶液，扫描速率设定为200 mV·s-1。在最佳检测条件下，制备的多巴胺电化学传感器电流的大小随着多巴胺浓度的增大而增大，在1.0×10-3~3.5×10-3 mol·L-1范围内呈现良好的线性关系，线性回归方程为I=8.120 6C+7.017，相关系数R2为0.999 5。且该传感器精密度好，稳定性强，具有一定的抗干扰能力。研究结果为药物盐酸多巴胺注射液中多巴胺含量测定提供了支撑。