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This study addresses the challenges of matrix effects and interspecies plasma protein binding (PPB) on measurement variability during method validation across diverse plasma types (human, rat, rabbit, and bovine). Accurate measurements of small molecules in plasma samples often require matrix-matched calibration approaches with the use of specific plasma types, which may have limited availability or affordability. To mitigate the costs associated with human plasma measurements, we explore in this work the potential of cross-matrix-matched calibration using Bayesian hierarchical modeling (BHM) to correct for matrix effects associated with PPB. We initially developed a targeted quantitative approach utilizing biocompatible solid-phase microextraction coupled with liquid chromatography-mass spectrometry for xenobiotic analysis in plasma. The method was evaluated for absolute matrix effects across human, bovine, rat, and rabbit plasma comparing pre- and postmatrix extraction standards. Absolute matrix effects from 96 to 108% for most analytes across plasma sources indicate that the biocompatibility of the extraction phase minimizes interference coextraction. However, the extent of PPB in different media can still affect the accuracy of the measurement when the extraction of small molecules is carried out via free concentration, as in the case of microextraction techniques. In fact, while matrix-matched calibration revealed high accuracy, cross-matrix calibration (e.g., using a calibration curve generated from bovine plasma) proved inadequate for precise measurements in human plasma. A BHM was used to calculate correction factors for each analyte within each plasma type, successfully mitigating the measurement bias resulting from diverse calibration curve types used to quantify human plasma samples. This work contributes to the development of cost-effective, efficient calibration strategies for biofluids. Leveraging easily accessible plasma sources, like bovine plasma, for method optimization and validation prior to analyzing costly plasma (e.g., human plasma) holds substantial advantages applicable to biomonitoring and pharmacokinetic studies., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

A series of strong, rebondable polydisulfide nanocomposite adhesive films have been prepared via the oxidation of a thiol-endcapped semicrystalline oligomer with varying amounts of thiol-functionalized cellulose nanocrystals (CNC-SH). The nanocomposites are designed to have two temperature-sensitive components: (1) the melting of the semicrystalline phase at ca. 70 °C and (2) the inherent dynamic behavior of the disulfide bonds at ca. 150 °C. The utility of these adhesives was demonstrated on different bonding substrates (hydrophilic glass slides and metal), and their bonding at both 80 and 150 °C was examined. In all cases, stronger bonding was achieved at temperatures where the disulfide bonds are dynamic. For high surface energy substrates, such as hydrophilic glass or metal, the adhesive shear strength increases with CNC-SH content, with the 30 wt % CNC-SH composites exhibiting adhesive shear strengths of 50 and 23 MPa for hydrophilic glass and metal, respectively. The effects of contact pressure and time of bonding were also investigated. It was found that ca. 20-30 min bonding time was required to reach maximum adhesion, with adhesives containing higher wt % CNCs requiring longer bonding times. Furthermore, it was found that, in general, an increase in contact pressure results in an increase in the shear strength of the adhesive. The rebonding of the adhesives was demonstrated with little-to-no loss in adhesive shear strength. In addition, the 30 wt % nanocomposite adhesive was compared to some common commercially available adhesives and showed significantly stronger shear strengths when bonded to metal.

An electrochemical process has been used to compact cellulose nanocrystals (CNC) and access aligned micron-sized CNC fibers. Placing a current across aqueous solutions of carboxylic acid functionalized CNCs (t-CNC-COOH) or carboxylic acid/primary amine functionalized CNCs (t-CNC-COOH-NH 2 ) creates a pH gradient between the electrodes, which results in the migration and concentration of the CNC fibers at their isoelectric point. By matching the carboxylic acid/amine ratio of CNCs and collagen (ca. 30:70 carboxylic acid:amine ratio), it is possible to coelectrocompact both nanofibers and access aligned nanocomposite fibers. t-CNC-COOH-NH 2 /collagen fibers showed a maximum increase in mechanical properties at 5 wt % of t-CNC-COOH-NH 2 . Compared to collagen/CNC films which have no alignment in the plane of the films, the tensile properties of the aligned fibers show a significant enhancement in the wet mechanical properties (40 MPa vs 230 MPa) for the 5 wt % of t-CNC-COOH-NH 2 /collagen films and fiber, respectively.

The dissociation dynamics of internal energy selected iron pentacarbonyl cations, Fe(CO)5(+), have been investigated using the imaging photoelectron photoion coincidence (iPEPICO) spectrometer at the Swiss Light Source. The molecular ion loses all five carbonyl ligands in sequential dissociations in the 8.5-20 eV photon energy range. The Fe(CO)5(+) parent ion is metastable at the onset of the first dissociation reaction on the time scale of the experiment. The slightly asymmetric and broad daughter ion time-of-flight distributions indicate parent ion lifetimes in the microsecond range, and are used to obtain an experimental dissociation rate curve. Further carbonyl losses were found to be fast at threshold. The fractional parent and daughter ion abundances as a function of the photon energy, that is, breakdown diagram, as well as the dissociation rates for the first CO loss were modeled using the statistical Rice-Ramsperger-Kassel-Marcus (RRKM) and statistical adiabatic channel model (SSACM) theories. The excess energy redistribution in the products was also taken into account in a statistical framework. The 0 K dissociative photoionization thresholds for the five carbonyl-loss channels were found to be 9.015 ± 0.024 eV, 10.199 ± 0.027 eV, 10.949 ± 0.033 eV, 12.282 ± 0.39 eV, and 13.821 ± 0.045 eV for the processes leading to Fe(CO)4(+), Fe(CO)3(+), Fe(CO)2(+), Fe(CO)(+), and Fe(+), respectively. The iron cation thermochemistry is well-known, and these onsets connect the bare metal ion to the other fragment ions as well as to the gas phase neutral Fe(CO)5.

A new configuration of C(18) thin film extraction phase designed for high sample throughput has been developed and applied to the analysis of benzodiazepines in spiked urine samples using high performance liquid chromatography coupled with tandem mass spectrometry. The high throughput analysis was achieved with the use of a robotic autosampler which enabled parallel analyte extraction in a 96-well plate format. Factors affecting data reproducibility, extraction kinetics, sample throughput, and reliability of the system were investigated and optimized. The intrawell reproducibility was 4.5-7.3%, while interwell reproducibility was 7.0-11% in urine and PBS samples. The limits of detection and quantitation were 0.05-0.15 ng/mL and 0.2-2.0 ng/mL for all analytes, respectively. By comparison with optimized automated multifiber SPME relying on rod geometry, the C(18) thin films showed higher extraction rates (approximate 2-fold increase) and hence higher sample throughput because of the improved configuration and more effective agitation/mass transfer. In addition, this new configuration provided an extraction phase with greater surface area to volume ratio and greater extraction phase volume, which resulted in approximately 2-fold increase in the extraction capacity for diazepam compared with the extractions with automated multifiber SPME rod geometry. The results of this investigation demonstrated the advantages of using thin films to improve extraction kinetics and sensitivity of automated SPME methods for high performance liquid chromatography.

The automation of solid-phase microextraction (SPME) coupled to liquid chromatography-tandem mass spectrometry (LC-MS/MS) was accomplished using a 96 multiwell plate format, a SPME multifiber device, two orbital shakers, and a three-arm robotic system. Extensive optimization of the proposed setup was performed including coating selection, optimization of the fiber coating procedure, confirmation of uniform agitation in all wells, and the selection of the optimal calibration method. The system allows the use of pre-equilibrium extraction times with no deterioration in method precision due to reproducible timing of extraction and desorption steps and reproducible positioning of all fibers within the wells. The applicability of the system for the extraction of several common drugs is demonstrated. The optimized multifiber SPME-LC-MS/MS was subsequently fully validated for the high-throughput analysis of diazepam, lorazepam, nordiazepam, and oxazepam in human whole blood. The proposed method allowed the automated sample preparation of 96 samples in 100 min, which represents the highest throughput of any SPME technique to date, while achieving excellent accuracy (87-113%), precision (