Third-Generation Method for High-Throughput Quantification of Trace Palladium by Color or Fluorescence
Third-Generation Method for High-Throughput Quantification of Trace Palladium by Color or Fluorescence
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DOI：
10.1021/acs.oprd.9b00472
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发表时间：
2020-01-01
影响因子：
3.4
通讯作者：
Koide, Kazunori
中科院分区：
文献类型：
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作者：
Lukomski, Lydia;Pohorilets, Ivanna;Koide, Kazunori
由于钯广泛应用于有机合成化学中，化学家经常遇到与合成样品中痕量钯有关的问题。我们以前报道了一种用于微量钯定量的比色法，这是制药行业中唯一实现的高通量方法。然而，从公布的反应条件的轻微变化引起了重现性问题，与基本的分子机制的了解很少。在目前的研究中，我们采取了一种组合方法来研究该方法，发现过量的NaOH是缺乏重现性的罪魁祸首。我们相应地改变了反应条件和程序，这大大提高了重现性。在当前条件下的反应遵循Michaelis-Menten动力学，允许基于底物浓度预测反应速率。目前的方法显示57%和72%的平均误差，分别与已知量的钯和合成样品与未知量的钯加标药物进行分析。通过当前方法测定的钯浓度的趋势与实际钯浓度很好地吻合。
Chemists frequently encounter problems associated with trace palladium in synthetic samples because palladium is widely used in synthetic organic chemistry. We previously reported a colorimetric method for trace palladium quantification, the only high-throughput method implemented in the pharmaceutical industry. However, slight changes from the published reaction conditions have caused reproducibility problems, with little understanding of underlying molecular mechanisms. In the current study, we took a combinatorial approach to investigate the method and found that excess NaOH was a culprit for the lack of reproducibility. We changed the reaction conditions and procedure accordingly, which substantially improved reproducibility. The reaction under current conditions followed Michaelis-Menten kinetics, allowing for predicting reaction rates on the basis of the substrate concentrations. The current method showed 57 and 72% average error, respectively, when drugs spiked with known amounts of palladium and synthetic samples with unknown amounts of palladium were analyzed. The trend of palladium concentrations determined by the current method boded well with actual palladium concentrations.