Third-Generation Method for High Throughput Quantification of Trace Palladium by Color or Fluorescence

Chemists frequently encounter problems associated with trace palladium in synthetic samples because palladium is presumably the most frequently used transition metal 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 strong basicity was a culprit for the lack of reproducibility. We changed the reaction conditions and procedure accordingly, which substantially improved reproducibility. We discovered that the reaction followed Michaelis-Menten kinetics, allowing for predicting reaction rates on the basis of the substrate concentrations. The current method showed good correlation with inductively coupled plasma mass spectroscopy when 14 synthetic samples with unknown amounts of trace palladium were quantified.