Rapid Analysis of Residual Palladium in Pharmaceutical Development Using a Catalysis-Based Fluorometric Method
Rapid Analysis of Residual Palladium in Pharmaceutical Development Using a Catalysis-Based Fluorometric Method
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DOI：
10.1021/op3003008
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发表时间：
2013-01-01
影响因子：
3.4
通讯作者：
Welch, Christopher J.
中科院分区：
文献类型：
--
作者：
Bu, Xiaodong;Koide, Kazunori;Welch, Christopher J.
通常使用电感耦合等离子体发射光谱法（ICP-OES）或电感耦合等离子体质谱法（ICP-MS）测量药物中间体中的残留金属。然而，这些技术具有限制其在制药工艺开发中的效用的缺点，包括需要昂贵的仪器、复杂的样品制备、缓慢的周转时间、有限的样品通量以及难以在中试工厂或制造环境内的“现场”进行所需的测量。我们研究了使用一种快速和廉价的高通量方法检测残留钯（Pd），基于Pd催化的烯丙基醚底物的Tsuji-Trost脱烯丙基化产生高荧光产物。我们证明了这种荧光分析的有效性，在各种“真实的世界”的样品，包括含有强钯配体的混合氧化态样品中的钯水平的准确定量。
Measurement of residual metals in pharmaceutical intermediates is routinely performed using inductively coupled plasma-optical emission spectroscopy (ICP-OES) or inductively coupled plasma-mass spectrometry (ICP-MS). However, these techniques suffer from drawbacks that limit their utility in pharmaceutical process development, including the requirement for expensive instrumentation, complex sample preparation, slow turnaround time, limited sample throughput, and the difficulty of performing the required measurements on the 'spot' within pilot plants or manufacturing environments. We investigate the use of a fast and inexpensive high-throughput approach for detection of residual palladium (Pd), based on the Pd-catalyzed Tsuji-Trost deallylation of an allylic ether substrate to produce a highly fluorescent product. We demonstrate the effectiveness of this fluorescence assay for accurate quantitation of Pd levels in a variety of 'real world' samples, including mixed oxidation-state samples containing strong Pd ligands.