Field-assisted paper spray mass spectrometry for the quantitative evaluation of imatinib levels in plasma

Drug levels in patients' bloodstreams vary among individuals and consequently therapeutic drug monitoring (TDM) is fundamental to controlling the effective therapeutic range. For TDM purposes, different analytical approaches have been used, mainly based on immunoassay, liquid chromatography-ultraviolet, liquid chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. More recently a matrix-assisted laser desorption/ionisation method has been proposed for the determination of irinotecan levels in the plasma of subjects under therapy and this method has been cross-validated by comparison with data achieved by LC-MS/MS. However, to reach an effective point-of-care monitoring of plasma drug concentrations, a TDM platform technology for fast, accurate, low-cost assays is required. In this frame, recently the use of paper spray mass spectrometry, which is becoming a popular and widely employed MS method, has been proposed. In this paper we report the results obtained by the development of a paper spray-based method for quantitative analysis in plasma samples of imatinib, a new generation of anticancer drug. Preliminary experiments showed that poor sensitivity, reproducibility and linear response were obtained by the "classical" paper spray set-up. In order to achieve better results, it was thought of interest to operate in presence of a higher and more homogeneous electrical field. For this aim, a stainless steel needle connected with the high voltage power supply was mounted below the paper triangle. Furthermore, in order to obtain valid quantitative data, we analysed the role of the different equilibria participating to the phenomena occurring in paper spray experiments, depending either on instrumental parameters or on the chemical nature of analyte and solvents. A calibration curve was obtained by spiking plasma samples containing different amounts of imatinib (1) with known amounts of deuterated imatinib (1d3) as internal standard, with molar ratios [1]/[1d3] in the range 0.00-2.00. A quite good linearity was obtained (R2 = 0.975) and some experiments performed on spiked plasma samples with known amounts of 1 confirmed the validity of this method

Glial fibrillary acidic protein plasma levels are correlated with degree of hypothermia during cardiopulmonary bypass in congenital heart disease surgery

OBJECTIVES: Improved congenital heart defect (CHD) operations have reduced operative mortality to 3%. The major concern is now long-term neurological outcomes. We measured plasma glial fibrillary acidic protein (GFAP), an early marker of brain injury, during different phases of cardiopulmonary bypass (CPB), to correlate the increase of GFAP to clinical parameters or specific operative phases. METHODS: We performed a prospective, single-centre, observational study in children undergoing cardiac operations. We studied 69 children with CHD and biventricular heart physiology: 26 had tetralogy of Fallot; 17 transposition of the great arteries; and 26 ventricular/ atrial septal defects with or without associated arch defects. GFAP levels were measured by ELISA at different stages of CPB. We recorded clinical and surgical parameters and applied multivariable and logistic regressions to assess which parameters were independent predictors of variations in plasma GFAP. RESULTS: GFAP increased during CPB and peaked at the end of rewarming. Multivariable regression showed degree of hypothermia as the only significant independent predictor of GFAP increase, adjusted for age, prematurity, type of CHD, cyanosis, aortic cross-clamp time, haemodilution, neurological risk time interval and rewarming rate. Temperature nadir and neurological risk time interval were significant independent predictors of a GFAP value > 0.46 ng/ml. CONCLUSIONS: Hypothermia degree during CPB is correlated with GFAP plasma increase in children with biventricular heart defects undergoing surgical repair. Rewarming is the most critical CPB phase for GFAP increase. The implication of high plasma GFAP is still under evaluation. Follow-up studies are ongoing to assess the reliability of GFAP as a marker of brain injury and/or as a predictor of neurodevelopmental abnormalities

Analytical aspects of sunitinib and its geometric isomerism towards therapeutic drug monitoring in clinical routine

Sunitinib malate, an oral multi-targeted tyrosine kinase inhibitor approved for the treatment of metastatic renal cell carcinoma, gastrointestinal stromal tumor, and well-differentiated pancreatic neuroendocrine tumors, has been identified as a potential candidate for therapeutic drug monitoring approach. Nevertheless, the development of an analytical assay suitable for clinical application for the quantification of the plasma concentration of sunitinib and its active metabolite, N-desethyl sunitinib, is limited by its Z/E isomerization when exposed to light. Several LC–MS/MS methods already published require protection from light during all sample handling procedures to avoid the formation of E-isomer, which makes them not suitable for clinical practice. In order to obtain a simple and fast procedure to reconvert the E-isomer, formed during sample collection and treatment without light protection, and, thus, to have only Z-isomer peak to quantify, we studied the Z/E photodegradation with special attention to the condition allowing the reverse reaction in plasma matrix. After 30 min of light exposure, the E-isomer maximum percentage of both the analytes was reached (44% of E-sunitinib and 20% of E-N-desethyl sunitinib; these percentages were calculated with respect to the sum of E + Z). Moreover, the formation of the E-isomer increased up to 20% after lowering the pH of the solution. Since the reverse reaction takes place when the pre-exposed solution is placed in dark, we followed the E to Z-isomer kinetics into the autosampler. The conversion rate was very slow when the autosampler was set at 4 °C (after 4 h the mean percentages of E-isomer were 50% for sunitinib and 22% for N-desethyl sunitinib). The reconversion rate was considerably accelerated with the increasing of the temperature: incubating the analytical solution in a heated water bath for 5 min at 70 °C we obtained the quantitative (99%) reconversion of the E- to the Z-isomer. No effect of concentration was observed, while the presence of acids inhibited the reconversion. Based on these results, a simple and fast procedure was setup to quantitatively reconvert the E-isomer formed during sample collection and processing without light protection into its Z-form thus leading to a single peak to quantify. The application of this additional step allows to develop a LC–MS/MS method suitable to clinical practice, due to its practicality and speed

Metal speciation of volcanic aerosols from Mt. Etna at varying aerosol water content and pH obtained by different thermodynamic models

Metal speciation of volcanic aerosol from Mt Etna, an open vent, persistently degassing volcano in Europe.The EPL-REFLECT campaign was funded by the European Commission under the EUROVOLC grant (Programme: Horizon2020, Grant number: 731070). This work was funded by the Supporting TAlent in ReSearch@University of Padova STARS-StG MOCAA awarded by the University of Padova to CG and a BP Next Generation fellowship awarded by the Yusuf Hamied Department of Chemistry at the University of Cambridge to CG

The Herbarium 2021 Half-Earth Challenge Dataset and Machine Learning Competition

Herbarium sheets present a unique view of the world's botanical history, evolution, and biodiversity. This makes them an all-important data source for botanical research. With the increased digitization of herbaria worldwide and advances in the domain of fine-grained visual classification which can facilitate automatic identification of herbarium specimen images, there are many opportunities for supporting and expanding research in this field. However, existing datasets are either too small, or not diverse enough, in terms of represented taxa, geographic distribution, and imaging protocols. Furthermore, aggregating datasets is difficult as taxa are recognized under a multitude of names and must be aligned to a common reference. We introduce the Herbarium 2021 Half-Earth dataset: the largest and most diverse dataset of herbarium specimen images, to date, for automatic taxon recognition. We also present the results of the Herbarium 2021 Half-Earth challenge, a competition that was part of the Eighth Workshop on Fine-Grained Visual Categorization (FGVC8) and hosted by Kaggle to encourage the development of models to automatically identify taxa from herbarium sheet images