Evaluation of propylene glycol methyl ether as a potential challenge agent for leak detection of liquid and headspace from closed system drug transfer devices using Fourier transform infrared spectroscopy.

Choosing an appropriate surrogate of hazardous drugs for use in testing Closed System Drug-Transfer Devices (CSTDs) is a challenging endeavor with many factors that must be considered. It was suggested that the compound propylene glycol methyl ether (PGME) may meet many of the criteria we considered important in a suitable surrogate. Criteria included sufficient volatility to evaporate from aqueous liquid leaks efficiently, a Henry's constant which produced sufficient vapor phase concentrations to make headspace leaks detectable, and suitability for detection using a low-cost detection system. We evaluated the measurement of vapors from solutions containing PGME released inside a closed chamber. We present data used to quantify limits of detection, limits of quantification, bias, precision, and accuracy of Fourier Transform Infrared Spectroscopy (FTIR) measurements of vapors from 2.5 M PGME solutions. The effects of ethanol as a component of the PGME solution were also evaluated. Liquid drops of PGME solutions and headspace vapors above PGME solutions were released to simulate leaks from CSTDs. Using a calibration apparatus, an instrumental limit of detection (LOD) of 0.25 ppmv and a limit of quantitation (LOQ) of 0.8 ppmv were determined for PGME vapor. A LOD of 1.1 µL and a LOQ of 3.5 µL were determined for liquid aliquots of 2.5 M PGME solution released in a closed chamber. Accurate quantitation of liquid leaks required complete evaporation of droplets. With the upper end of the useable quantitation range limited by slow evaporation of relatively large droplets and the lower end defined by the method LOQ, the method evaluated in this research had a narrow quantitative range for liquid droplets. Displacement of 45 mL of vial headspace containing PGME vapor is the largest amount expected when using the draft NIOSH testing protocol. Release of an unfiltered 45 mL headspace aliquot within the NIOSH chamber was calculated to produce a concentration of 0.8 ppmv based on the Henry's constant, which is right at the instrumental LOQ. Therefore, the sensitivity of the method was not adequate to determine leaks of PGME vapor from a headspace release through an air filtering CSTD when using the draft NIOSH testing protocols with an FTIR analyzer.

Plasmon-enhanced triplet-triplet annihilation upconversion of post-modified polymeric acceptors.

We report the localized surface plasmon resonance (LSPR)-enhanced triplet-triplet annihilation upconversion (TTA-UC) of polymeric acceptors containing high percentages of acceptor units. A poly[(methyl methacrylate)-co-(glycidyl methacrylate)] copolymer series with increasing glycidyl methacrylate ratio was prepared using reversible addition-fragmentation chain transfer (RAFT) polymerization. After post-modification of the glycidyl group with anthracene, the acceptor unit, a series of poly[(methyl methacrylate)-co-(2-hydroxypropyl-9-anthroate methacrylate)] (polyACA) was produced with different numbers of acceptor units. These polymeric acceptors were grafted to silver nanoparticles in order to enhance the TTA-UC intensity in the polymers with higher percentages of acceptor units, where concentration quenching usually dominates. With the assistance of the silver nanoparticle LSPR, TTA-UC intensity was enhanced from the polymeric acceptor nanocomposites using platinum octaethylporphyrin as the sensitizer to form the TTA-UC systems. This method is anticipated to improve TTA-UC in the solid-state, where higher percentages of acceptor units are required, but usually cause chromophore concentration quenching, reducing TTA-UC efficiency.

Acidotoxicity via ASIC1a Mediates Cell Death during Oxygen Glucose Deprivation and Abolishes Excitotoxicity.

Ischemic reperfusion (I/R) injury is associated with a complex and multifactorial cascade of events involving excitotoxicity, acidotoxicity, and ionic imbalance. While it is known that acidosis occurs concomitantly with glutamate-mediated excitotoxicity during brain ischemia, it remains elusive how acidosis-mediated acidotoxicity interacts with glutamate-mediated excitotoxicity. Here, we investigated the effect of acidosis on glutamate-mediated excitotoxicity in acute hippocampal slices. We tested the hypothesis that mild acidosis protects against I/R injury via modulation of NMDAR, but produces injury via activation of acid sensing ion channels (ASIC1a). Using a novel microperfusion approach, we monitored time course of injury in acutely prepared, adult hippocampal slices. We varied the duration of insult to delay the return to preinsult conditions to determine if injury was caused by the primary insult or by the modeled reperfusion phase. We also manipulated pH in presence and absence of oxygen glucose deprivation (OGD). The role of ASIC1a and NMDAR was deciphered by treating the slices with and without an ASIC or NMDAR antagonist. Our results show that injury due to OGD or low pH occurs during the insult rather than the modeled reperfusion phase. Injury mediated by low pH or low pH OGD requires ASIC1a and is independent of NMDAR activation. These findings point to ASIC1a as a mediator of ischemic cell death caused by stroke and cardiac arrest.