Formation of copper(I) from trace levels of copper(II) as an artifactual impurity in the HPLC analysis of olanzapine

Baertschi, Steven W.; Olsen, Bernard A.; Wozniak, Timothy J.; Toltl, Nick; O’Shea, Colette; Jansen, Patrick J.

doi:10.1016/j.jpba.2016.03.040

Cited by 9 publications

(2 citation statements)

References 12 publications

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“…Additionally, we found that such on-column degradation had been mainly observed in CXA-TFA samples (typical level of Pd: 100 ppm) compared to CXA-sulfate (typical level of Pd: 1–5 ppm), which strongly suggested that the on-column conversion was related to the level of Pd in the samples. This led to the hypothesis that the oxidizing species were Pd-complexes with or without additional redox-active co-oxidant or cocatalyst. − This hypothesis can also be supported by recent reports where a trace amount of metal contamination causes on-column degradation in HPLC analysis. − …”

Section: Introductionmentioning

confidence: 77%

Metal Speciation in Pharmaceutical Process Development: Case Studies and Process/Analytical Challenges for a Palladium-Catalyzed Cross-Coupling Reaction

Xiang

et al. 2018

Organometallics

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Transition metal catalysts in pharmaceutical processes is widely used, but health care agencies such as the Food and Drug Administration and the European Medicines Agency highly regulate the residual level of elemental impurities in the final drug substance and drug product to avoid any adverse effect on patients. Controlling these elemental impurities requires a thorough understanding of the catalytic mechanism and the fate of each elemental impurity. Only with this knowledge in hand can a process be developed to sufficiently remove residual elemental impurities to acceptable levels. Recently, there has been tremendous progress in metal speciation directly assisted by HPLC-ICP-MS. To investigate the removal of elemental impurities from reaction process, we have utilized metal speciation data to provide critical information on the fate of each elemental impurity and a deeper understanding of the catalytic mechanism. Herein we present our recent analytical showcases on (i) how we successfully implemented analytical methods such as HPLC-ICP-MS and HPLC-ESI-TOF-MS to understand and quantify metal species in process development, (ii) how such analytical tools provided a guidance to control residual palladium down to less than 1 ppm level in drug substance, and (iii) how uncontrolled metallic impurities can cause analytical challenges including on-column degradation.

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Section: Introductionmentioning

confidence: 77%

Metal Speciation in Pharmaceutical Process Development: Case Studies and Process/Analytical Challenges for a Palladium-Catalyzed Cross-Coupling Reaction

Xiang

et al. 2018

Organometallics

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“…The sources of these "ghost peaks" include sample degradation, instrumentation, solvents, glassware, and closure systems [4]. Recently, several groups reported that analytical solution degradation caused by non-obvious reasons was one of the contributing factors for inducing such "ghost peaks" [5][6][7][8]. The behavior of the unknown peak presented at RRT 1.60 in brexpiprazole renders itself another case of ghost peak occurrence.…”

Section: Introductionmentioning

confidence: 99%

“Ghost Peak” Driven Structural Elucidation of a Photocatalytic Degradation Product from Brexpiprazole

Zhuang

Li³

et al. 2019

Preprint

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Brexpiprazole which marketed as Rexulti® is a second-generation atypical antipsychotic. A seemingly random and uncontrollable “ghost peak” that vary from below the detection limit to ∼0.2% was observed occasionally during the development of HPLC method for brexpiprazole drug substance. The “ghost peak” was finally characterized as a syn head-to-tail dimer of brexpiprazole by UV, IR, LC–MS/TOF, 1D and 2D NMR. It was formed rapidly through photocatalytic [2 + 2] pericyclic reaction and can reach approximately 1.7% in five minutes once the analytes were exposed to sunlight at noon. By contrast, the occurrence of this “ghost peak” in brexpiprazole can be suppressed when the solutions were prepared and stored away from sunlight.

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All-in-one strategy for the nano-engineering of paper-based bifunctional fluorescent platform for robustly-integrated real-time monitoring of food and drinking-water safety

Jiang,

Zhang,

et al. 2024

Journal of Hazardous Materials

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Formation of copper(I) from trace levels of copper(II) as an artifactual impurity in the HPLC analysis of olanzapine

Cited by 9 publications

References 12 publications

Metal Speciation in Pharmaceutical Process Development: Case Studies and Process/Analytical Challenges for a Palladium-Catalyzed Cross-Coupling Reaction

Metal Speciation in Pharmaceutical Process Development: Case Studies and Process/Analytical Challenges for a Palladium-Catalyzed Cross-Coupling Reaction

“Ghost Peak” Driven Structural Elucidation of a Photocatalytic Degradation Product from Brexpiprazole

All-in-one strategy for the nano-engineering of paper-based bifunctional fluorescent platform for robustly-integrated real-time monitoring of food and drinking-water safety

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