Analytical Performance Evaluation of New DESI Enhancements for Targeted Drug Quantification in Tissue Sections

Desorption/ionization (DI)-mass spectrometric (MS) methods offer considerable advantages of rapidity and low-sample input for the analysis of solid biological matrices such as tissue sections. The concept of desorption electrospray ionization (DESI) offers the possibility to ionize compounds from solid surfaces at atmospheric pressure, without the addition of organic compounds to initiate desorption. However, severe drawbacks from former DESI hardware stability made the development of assays for drug quantification difficult. In the present study, the potential of new prototype source setups (High Performance DESI Sprayer and Heated Transfer Line) for the development of drug quantification assays in tissue sections was evaluated. It was demonstrated that following dedicated optimization, new DESI XS enhancements present promising options regarding targeted quantitative analyses. As a model compound for these developments, ulixertinib, an inhibitor of extracellular signal-regulated kinase (ERK) 1 and 2 was used

Approaching Sites of Action of Temozolomide for Pharmacological and Clinical Studies in Glioblastoma

Temozolomide (TMZ), together with bulk resection and focal radiotherapy, is currently a standard of care for glioblastoma. Absorption, distribution, metabolism, and excretion (ADME) parameters, together with the mode of action of TMZ, make its biochemical and biological action difficult to understand. Accurate understanding of the mode of action of TMZ and the monitoring of TMZ at its anatomical, cellular, and molecular sites of action (SOAs) would greatly benefit precision medicine and the development of novel therapeutic approaches in combination with TMZ. In the present perspective article, we summarize the known ADME parameters and modes of action of TMZ, and we review the possible methodological options to monitor TMZ at its SOAs. We focus our descriptions of methodologies on mass spectrometry-based approaches, and all related considerations are taken into account regarding the avoidance of artifacts in mass spectrometric analysis during sampling, sample preparation, and the evaluation of results. Finally, we provide an overview of potential applications for precision medicine and drug development

Analytical Performance Evaluation of New DESI Enhancements for Targeted Drug Quantification in Tissue Sections

Desorption/ionization (DI)-mass spectrometric (MS) methods offer considerable advantages of rapidity and low-sample input for the analysis of solid biological matrices such as tissue sections. The concept of desorption electrospray ionization (DESI) offers the possibility to ionize compounds from solid surfaces at atmospheric pressure, without the addition of organic compounds to initiate desorption. However, severe drawbacks from former DESI hardware stability made the development of assays for drug quantification difficult. In the present study, the potential of new prototype source setups (High Performance DESI Sprayer and Heated Transfer Line) for the development of drug quantification assays in tissue sections was evaluated. It was demonstrated that following dedicated optimization, new DESI XS enhancements present promising options regarding targeted quantitative analyses. As a model compound for these developments, ulixertinib, an inhibitor of extracellular signal-regulated kinase (ERK) 1 and 2 was used

Observation of the decay B‾s0→χc2K+K− {\overline{B}}_s^0\to {\chi}_{c2}{K}^{+}{K}^{-} in the ϕ\phi mass region

The $\overline{B_s^0} \rightarrow \chi_{c2} K^+ K^-$ decay mode is observed and its branching fraction relative to the corresponding $\chi_{c1}$ decay mode, in a $\pm 15 \textrm{MeV}/c^2$ window around the $\phi$ mass, is found to be $\frac{\mathcal{B}(\overline{B_s^0} \rightarrow \chi_{c2} K^+ K^-) }{ \mathcal{B}(\overline{B_s^0} \rightarrow \chi_{c1} K^+ K^-)} = (17.1 \pm 3.1 \pm 0.4 \pm 0.9)\%,$ where the first uncertainty is statistical, the second systematic and the third due to the knowledge of the branching fractions of radiative $\chi_c$ decays. The decay mode $\overline{B_s^0} \rightarrow \chi_{c1} K^+ K^-$ allows the $B_s^0$ mass to be measured as $m(B_s^0) = 5366.83 \pm 0.25 \pm 0.27 \, \textrm{MeV}/c^2,$ where the first uncertainty is statistical and the second systematic. A combination of this result with other LHCb determinations of the $B_s^0$ mass is made