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

Abstract

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.

Catalysis-Based Fluorometric Method for Trace Palladium Detection with Improved Convenience

“…27,30 RAE may be more convenient than allyl Pittsburgh Green ether because the RAE method provides both colorimetric and fluorometric measurements and visualization. We previously published three variants with RAE, 27,31,35 and the first-generation method has been routinely practiced at Merck Research Laboratories. These methods had shortcomings: first, sodium borohydride in aqueous sodium hydroxide (Figure 1b) is difficult to use.…”

“…46 Additionally, sodium hydroxide reacts with RAE if the pH is not adjusted properly, generating false data. 35 Sodium hydroxide cannot be omitted because sodium borohydride in nonbasic water degrades within a few hours. 35 Therefore, a solution of sodium borohydride in aqueous sodium hydroxide must be prepared on the same day for reproducible results.…”

Continuous Hydrogenation: Triphasic System Optimization at Kilo Lab Scale Using a Slurry Solution

“…Another main point of the slurry is the presence of the catalyst in the liquid. On the other hand, it needs an adequate filtering/removal system (Recho et al, 2014) as the presence of metals in the product is problematic in the pharmaceutical industry (Garrett and Prasad 2004) and requires removal and analytical method (Lukomski et al, 2020;Williams et al, 2020). This can be achieved with resin systems (for dissolved metal species) (Barbaras et al, 2009;Phillips et al, 2016) and subsequently filtration (Ottoboni et al, 2019).…”

A fluorescent probe for the discrimination of oxidation states of palladium

“…2a, S1 and S2 ‡). [19][20][21][22][23][24][25]34 Increase of the coumarin uorescence is time-dependent, a bar graph describing changes of uorescence intensity over time is shown in Fig. 2b.…”

“…For example, two uorescent rotaxane probes have been recently identied in Goldup's group as a selective Zn 2+ and Pt 2+ sensor. 17,18 As for palladium, there are also numerous probes designed for detecting Pd 0 (sometimes appeared as Pd 2+ with reducing agents such as carbon monoxide and sodium borohydride) [19][20][21][22][23][24][25] or Pd 2+ . [26][27][28][29][30][31] However, to the best of our knowledge, very few reports have described the discrimination of Pd 0 and Pd 2+ within one uorescent probe.…”