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.

A field-portable colorimetric method for the measurement of peracetic acid vapors: a comparison of glass and plastic impingers.

A method for measuring peracetic acid vapors in air using impinger sampling and field-portable colorimetric analysis is presented. The capture efficiency of aqueous media in glass and plastic impingers was evaluated when used for peracetic acid vapor sampling. Measurement of peracetic acid was done using an N,N-diethyl-p-phenylenediamine colorimetric method with a field-portable spectrometer. The linearity of the N,N-diethyl-p-phenylenediamine method was determined for peracetic acid both in solution and captured from vapor phase using glass or plastic impingers. The Limits of Detection for the glass and plastic impingers were 0.24 mg/m3 and 0.28 mg/m3, respectively, for a 15 L air sample. The Limits of Quantitation were 0.79 mg/m3 and 0.92 mg/m3 for the glass and plastic impingers, respectively. Both metrics were below the American Conference of Governmental Industrial Hygienists Threshold Limit Value Short-Term Exposure Limit of 1.24 mg/m3 (0.4 ppmv) during a 15-min period. The impinger sampling method presented herein allows for an easy-to-use and rapid in-field measurement that can be used for evaluating occupational exposure to peracetic acid.

Source apportionment and quantification of liquid and headspace leaks from closed system drug-transfer devices via Selected Ion Flow Tube Mass Spectrometry (SIFT-MS).

A system to differentiate and quantify liquid and headspace vapor leaks from closed system drug-transfer devices (CSTDs) is presented. CSTDs are designed to reduce or eliminate hazardous drug (HD) exposure risk when compounding and administering HDs. CSTDs may leak liquid, headspace, or a mixture of the two. The amount of HD contained in liquid and headspace leaks may be substantially different. Use of a test solution containing two VOCs with differences in ratios of VOC concentrations in the headspace and liquid enables source apportionment of leaked material. SIFT-MS was used to detect VOCs from liquid and headspace leaks in the vapor phase. Included in this report is a novel method to determine the origin and magnitude of leaks from CSTDs. A limit of leak detection of 24 µL of headspace vapor and 0.14 µL of test liquid were found using Selected Ion Flow Tube Mass Spectrometry (SIFT-MS).

Controlled generation of peracetic acid atmospheres for the evaluation of chemical samplers.

A system for controlled generation of peracetic acid (PAA) atmospheres used to test and evaluate sampling and measurement devices was developed and characterized. Stable atmospheric conditions were maintained in a dynamic flow system for hours while multiple sensors were simultaneously exposed to equivalent atmospheres of PAA vapors. Atmospheres characterized by a range of PAA concentrations at a controlled flow rate, temperature, and humidity were generated. Presented herein is a system for vaporization of PAA solutions to generate controlled atmospheres with less than 3% relative standard deviation (RSD) of the PAA concentrations over time.

Assessing flammable storage cabinets as sources of VOC exposure in laboratories using real-time direct reading wireless detectors.

Herein we present the results of measurements using wireless direct-reading photoionization detector-based gas sensors to quantify concentrations of vapors of volatile organic compounds (VOCs) in and around flammable storage cabinets containing common organic solvents, including acetone, dichloromethane, trichloroethylene, and benzene. Such cabinets are commonly employed in laboratories to contain flammable liquids. A sensor array was deployed in a series of flammable storage cabinets in working laboratories. Measurements in cabinets containing bottles of typical solvents demonstrate that vapor concentrations gradually increase upon closing the cabinet door. The results suggest that these storage units can be a source of vapors of VOCs in laboratories and the unnecessary exposure of laboratory workers to chemical vapors. Ventilation of cabinets tended to lower maximum concentrations of VOCs. However, the efficacy of this engineering control was found to depend on the quality of the cabinet door seal, as well as having debris-free flame arrestors. Opening cabinet doors resulted in release of vapors to the laboratory atmosphere, which represents an unnecessary exposure risk for workers. A countermeasure aimed at improving the seal of previously opened solvent bottles reduced measured concentrations of VOCs in cabinets below the detector's limit of detection.

A system for characterizing Mg corrosion in aqueous solutions using electrochemical sensors and impedance spectroscopy.

Understanding Mg corrosion is important to the development of biomedical implants made from Mg alloys. Mg corrodes readily in aqueous environments, producing H2, OH- and Mg2+. The rate of formation of these corrosion products is especially important in biomedical applications where they can affect cells and tissue near the implant. We have developed a corrosion characterization system (CCS) that allows realtime monitoring of the solution soluble corrosion products OH-, Mg2+, and H2 during immersion tests commonly used to study the corrosion of Mg materials. Instrumentation was developed to allow the system to also record electrochemical impedance spectra simultaneously in the same solution to monitor changes in the Mg samples. We demonstrated application of the CCS by observing the corrosion of Mg (99.9%) in three different corrosion solutions: NaCl, HEPES buffer, and HEPES buffer with NaCl at 37°C for 48 h. The solution concentrations of the corrosion products measured by sensors correlated with the results using standard weight loss measurements to obtain corrosion rates. This novel approach gives a better understanding of the dynamics of the corrosion process in realtime during immersion tests, rather than just providing a corrosion rate at the end of the test, and goes well beyond the immersion tests that are commonly used to study the corrosion of Mg materials. The system has the potential to be useful in systematically testing and comparing the corrosion behavior of different Mg alloys, as well as protective coatings.

Carbohydrate-based label-free detection of Escherichia coli ORN 178 using electrochemical impedance spectroscopy.

A label-free biosensor for Escherichia coli (E. coli) ORN 178 based on faradaic electrochemical impedance spectroscopy (EIS) was developed. α-Mannoside or ß-galactoside was immobilized on a gold disk electrode using a self-assembled monolayer (SAM) via a spacer terminated in a thiol functionality. Impedance measurements (Nyquist plot) showed shifts due to the binding of E. coli ORN 178, which is specific for α-mannoside. No significant change in impedance was observed for E. coli ORN 208, which does not bind to α-mannoside. With increasing concentrations of E. coli ORN 178, electron-transfer resistance (R(et)) increases before the sensor is saturated. After the Nyquist plot of E. coli/mixed SAM/gold electrode was modeled, a linear relationship between normalized R(et) and the logarithmic value of E. coli concentrations was found in a range of bacterial concentration from 10(2) to 10(3) CFU/mL. The combination of robust carbohydrate ligands with EIS provides a label-free, sensitive, specific, user-friendly, robust, and portable biosensing system that could potentially be used in a point-of-care or continuous environmental monitoring setting.

N-acetylaspartate as a reservoir for glutamate.

N-acetylaspartate (NAA) is an intermediary metabolite that is found in relatively high concentrations in the human brain. More specifically, NAA is so concentrated in the neurons that it generates one of the most visible peaks in nuclear magnetic resonance (NMR) spectra, thus allowing NAA to serve as "a neuronal marker". However, to date there is no generally accepted physiological (primary) role for NAA. Another molecule that is found at similar concentrations in the brain is glutamate. Glutamate is an amino acid and neurotransmitter with numerous functions in the brain. We propose that NAA, a six-carbon amino acid derivative, is converted to glutamate (five carbons) in an energetically favorable set of reactions. This set of reactions starts when aspartoacylase converts the six carbons of NAA to aspartate and acetate, which are subsequently converted to oxaloacetate and acetyl CoA, respectively. Aspartylacylase is found in astrocytes and oligodendrocytes. In the mitochondria, oxaloacetate and acetyl CoA are combined to form citrate. Requiring two steps, the citrate is oxidized in the Kreb's cycle to alpha-ketoglutarate, producing NADH. Finally, alpha-ketoglutarate is readily converted to glutamate by transaminating the alpha-keto to an amine. The resulting glutamate can be used by multiple cells types to provide optimal brain functional and structural needs. Thus, the abundant NAA in neuronal tissue can serve as a large reservoir for replenishing glutamate in times of rapid or dynamic signaling demands and stress. This is beneficial in that proper levels of glutamate serve critical functions for neurons, astrocytes, and oligodendrocytes including their survival. In conclusion, we hypothesize that NAA conversion to glutamate is a logical and favorable use of this highly concentrated metabolite. It is important for normal brain function because of the brain's relatively unique metabolic demands and metabolite fluxes. Knowing that NAA is converted to glutamate will be important for better understanding myriad neurodegenerative diseases such as Canavan's Disease and Multiple Sclerosis, to name a few. Future studies to demonstrate the chemical, metabolic and pathological links between NAA and glutamate will support this hypothesis.