一种用于生产[C]尼古丁的新型自动化循环方法的开发与优化。
Development and optimization of a novel automated loop method for production of [C]nicotine.
作者信息
Ghosh Arijit, Woolum Karen, Knopp Michael V, Kumar Krishan
机构信息
Laboratory for Translational Research in Imaging Pharmaceuticals, The Wright Center of Innovation in Biomedical Imaging, Department of Radiology, The Ohio State University, Columbus, OH 43212, United States.
Laboratory for Translational Research in Imaging Pharmaceuticals, The Wright Center of Innovation in Biomedical Imaging, Department of Radiology, The Ohio State University, Columbus, OH 43212, United States.
出版信息
Appl Radiat Isot. 2018 Oct;140:76-82. doi: 10.1016/j.apradiso.2018.05.030. Epub 2018 May 30.
A novel, rapid, and automated loop method for the synthesis of [C]nicotine was developed and optimized. The method involves, a reaction of the precursor, (+) nornicotine or (-) nornicotine, with a gas-phase produced [C]CHI in an 800 µL loop at 75 °C for 5 min followed by a semi-preparatory Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC) purification. The optimized synthesis and purification process was complete in < 30 min and produced [C]nicotine with > 99.9% Radiochemical Purity (RCP), no [C]CHI, no (+) nornicotine, 105 mCi/µmole specific activity, 7.0 - 7.2 pH, and 16.6% ethanol. The current method can be optimized, to reduce the ethanol content (<10%), and can be translated to a cGMP production of [C]nicotine for human clinical trials.
开发并优化了一种用于合成[C]尼古丁的新颖、快速且自动化的环法。该方法包括前体（(+)去甲烟碱或(−)去甲烟碱）与气相产生的[C]CHI在800微升环中于75°C反应5分钟，随后进行半制备反相高效液相色谱（RP-HPLC）纯化。优化后的合成和纯化过程在不到30分钟内完成，产生的[C]尼古丁具有>99.9%的放射化学纯度（RCP），无[C]CHI，无(+)去甲烟碱，比活度为105毫居里/微摩尔，pH值为7.0 - 7.2，乙醇含量为16.6%。当前方法可以进行优化以降低乙醇含量（<10%），并且可以转化为用于人体临床试验的[C]尼古丁的cGMP生产。
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