ANALYSIS OF OPIOID PEPTIDE ANALOGS

在这个项目的头三年中积累的经验 项目赠款清楚地表明有必要在三个不同的 这一分析化学部分的领域。 答：每种多肽的检测灵敏度将提高100倍， 1000倍，从皮摩尔到毫微摩尔水平。最近的初步调查 数据显示，该化合物的检测下限为60fmol。这一改进将使我们能够 以检测任何可能已转移到 胎儿，并将允许感染较少量的多肽进入 母亲。 B.在司徒和克拉普博士筛选了每一种合成阿片肽类似物后 以确定该阿片肽类似物是否具有适当的 生理活性，血浆样本将采集和多肽 量过了。经高效液相纯化后的多肽将与质量一起定量。 光谱(MS)。下面讨论了关于MS定量的数据 阿片肽类似物DALDA和DAMGO。相应的氢化氢 每种多肽的合成类似物(由席勒博士合成)将 用作MS定量的内标，也可作为载体 以提高从生物中回收该合成肽的能力 矩阵。这些分析数据将被用来得出相应的 药代动力学参数。 C.分析绵羊血浆样本的速度将提高10倍 通过采用新的固相萃取(SPE)色谱柱，可提高100倍的色谱峰。绵羊 血浆将直接应用，蛋白质沉淀将 避免了。

The experience gathered during the first three years of this program project grant clearly indicates the need for improvement in three separate areas for this analytical chemistry component. A. The detection sensitivity for each peptide will be improved 100-fold to 1000 fold, from the picomole to the femtomole level. Recent preliminary data show a limit of detection of 60 fmol. That improvement will enable us to detect any synthetic peptide that may have been transferred to the fetus, and will allow the infection of a smaller amount of peptide into the mother. B. After Drs. Szeto and Clapp screen each synthetic opioid peptide analog to determine whether that opioid peptide analog has appropriate physiologic activity, plasma samples will be collected and the peptide measured. The HPLC-purified peptide will be quantified with mass spectrometry (MS). Data are discussed below on the MS quantitation of the opioid peptide analogs DALDA and DAMGO. The corresponding deuterated synthetic analog of each peptide (synthesized by Dr. Schiller) will be used as the internal standard for MS quantification, and also as a carrier to increase the recovery of that synthetic peptide from the biological matrix. Those analytical data will be used to derive the corresponding pharmacokinetic parameters. C. The rate of analyzing ovine plasma samples will be improve 10-fold to 100-fold by employing new solid phase extraction (SPE) cartridges. Ovine plasma will be applied directly, and protein precipitation will be avoided.