Evaluation of a four-channel multiplexed electrospray triple quadrupole mass spectrometer for the simultaneous validation of LC/MS/MS methods in four different preclinical matrixes

A four-channel multiplexed electrospray interface on a triple quadrupole mass spectrometer was evaluated for the simultaneous validation of LC/MS/MS methods for the quantitation of loratadine and its metabolite, descarboethoxyloratadine, in four different biological matrixes. The assays were performed in rat, rabbit, mouse, and dog plasma from 1 to 1000 ng/mL using 96-well solid-phase extraction for sample preparation. The limit of quantitation of 1 ng/mL corresponded to 5.56 pg of each analyte injected on-column. For the drug, quality control samples (n = 6 at four concentrations) had precision ranging from 0.967 to 16.0% and accuracy ranging from -8.44 to 10.5% across all four species. For the metabolite, the precision ranged from 0.684 to 11.0% and the accuracy was between 6.36 and -9.06%. Intersprayer cross talk for the multiplexed electrospray ion source was evaluated as a function of analyte concentration and was less than 0.08% at concentrations as high as 1000 ng/mL. These results demonstrate the feasibility of using parallel analysis to reduce the time required for method validation and to increase sample throughput in drug development studies.     

Transition Metal Exchanged Zeolite Layers for Selectivity Enhancement of Metal-Oxide Semiconductor Gas Sensors

A novel method of improving the selectivity of metal oxide gas sensors has been developed by using catalytically active molecular sieve materials. They have been successfully introduced into a proprietary sensor array. The cracking patterns of linear alkanes over transition metal exchanged zeolite Y have been measured using a zeolite bed/GC/MS experimental set-up within a temperature range of 300degC to 400degC. Studies have been carried out regarding the effects of metal loading, zeolite type, material fabrication techniques, and operating temperature in relation to catalytic activity and selectivity. The composite sensors utilising the novel zeolite materials have been used in a custom built sensor rig that houses three dual electrode sensors and can measure real-time responses of these sensors to an introduced headspace generated from organic liquids     

Vaccine genotype and route of administration affect pseudorabies field virus latency load after challenge

The influence of vaccine genotype and route of administration on the efficacy of pseudorabies virus (PRV) vaccines against virulent PRV challenge was evaluated in a controlled experiment using five genotypically distinct modified live vaccines (MLVs) for PRV. Several of these MLVs share deletions in specific genes, however, each has its deletion in a different locus within that gene. Pigs were vaccinated with each vaccine, either via the intramuscular or intranasal route, and subsequently challenged with a highly virulent PRV field strain. During a 2-week period following challenge with virulent PRV, each of the vaccine strains used in this study was evaluated for its effectiveness in the reduction of clinical signs, prevention of growth retardation and virulent virus shedding. One month after challenge, tissues were collected and analyzed for virulent PRV latency load by a recently developed method for the electrochemiluminescent quantitation of latent herpesvirus DNA in animal tissues after PCR amplification. It was determined that all vaccination protocols provided protection against clinical signs resulting from field virus challenge and reduced both field virus shedding and latency load after field virus challenge. Our results indicated that vaccine efficacy was significantly influenced by the modified live vaccine strain and route of administration. Compared to unvaccinated pigs, vaccination reduced field virus latency load in trigeminal ganglia, but significant differences were found between vaccines and routes of administration. We conclude that vaccine genotype plays a role in the effectiveness of PRV MLVs.     

Boundary layer drug delivery using a helical catheter

BACKGROUND: A catheter-based approach for local endovascular drug delivery has been developed. The catheter is deployed percutaneously, while the end of the catheter is in the form of a helix that is placed just proximal to the vascular site to be treated. The helices are in contact with the vessel wall. A number of small holes is drilled in the coils of the catheter through which drug is infused, so that the infused drug remains within the blood fluid 'boundary layer' adjacent to the vessel wall. This approach is expected to be highly efficient for administration of antithrombotic and antiproliferative agents that target processes leading to vascular occlusion, heart attacks, and strokes. METHODS: The helical catheter was qualitatively evaluated using optical dye density measurements of Evans blue dye infused using an in vitro steady flow system under a physiologic range of conditions. To further demonstrate the efficiency of the technique, its capacity to inhibit thrombosis was evaluated in a baboon thrombosis model. The catheter was inserted into a femoral arteriovenous shunt (blood flow rate = 100 ml/min) and placed proximal to a segment of highly thrombogenic Dacron vascular graft (4.0 mm i.d.). Integrelin (an inhibitor of platelet glycoprotein IIb/IIIa; doses: 0.25-1.0 microg/min) and hirudin (an antithrombin; doses: 10-100 microg/min) were used to inhibit thrombus formation. RESULTS: Experimental flow visualization studies demonstrated that high concentrations of the infused Evans blue dye were retained near the vessel wall. In the animal experiments, platelet deposition on the Dacron graft surface was reduced by 82-97% (Integrelin) and 68-92% (hirudin) over 1-2 h of blood exposure. The local antithrombotic effects produced were found to be 200-fold and 30-fold more efficient than systemic administration of the same agents. CONCLUSIONS: Local drug infusion using the helical catheter approach can achieve high drug concentration levels at target sites, may avoid systemic effects, and can reduce cost of therapy by reducing total drug requirements.     

Analysis of solid renal dysplasia by flow cytometry: malignant potential?

The iron-chelating agent desferrioxamine now finds extensive use in the treatment and diagnosis of aluminum-related diseases in renal patients. We review the chemistry and pharmacokinetics of desferrioxamine in chelation therapy for patients on hemodialysis.     

Crossflow filtration testing of INEEL radioactive and non-radioactive waste slurries

Development of waste treatment processes for the remediation of radioactive wastes is currently under way at the Idaho Nuclear Technology and Engineering Center (INTEC), located at the Idaho National Engineering and Environmental Laboratory (INEEL). INTEC, formerly known as the Idaho Chemical Processing Plant, previously reprocessed nuclear fuel to retrieve fissionable uranium. Liquid waste raffinates resulting from reprocessing were solidified into a calcine material. Waste treatment processes currently being considered include the dissolution of the solidified calcine material and separation of residual undissolved solids (UDS). UDS in solution must be removed prior to downstream processes such as solvent extraction and ion exchange. Filtration experiments were conducted at the INEEL using a crossflow filter apparatus on radioactive and non-radioactive waste slurries [N.R. Mann, T.A. Todd, Evaluation and Testing of the Cells Units Crossflow Filter on INEEL Dissolved Calcine Slurries, INEEL/EXT-98-00749, Idaho National Engineering and Environmental Laboratory, Idaho Falls, ID, 1998]. The purpose of this testing was to evaluate the removal and operational efficiency of crossflow filtration on slurries of various solids loadings. The solids loadings tested were 0.19, 2.44 and 7.94 wt.%, respectively. A matrix of test patterns was used to determine the effects of transmembrane pressure and axial velocity on filtrate flux. Filtrate flux rates for each solids loading displayed a high dependence on transmembrane pressure, indicating that pressure filtration resistance limits filtrate flux. Filtrate flux rates for all solids loading displayed a negative dependency on axial velocity. This would suggest axial velocities tested were efficient at removing filter cake. Prior to testing of actual waste slurries, baseline water runs were performed. Filtrate flowrates observed during baseline water runs exhibited substantial decreases despite numerous backpulses and rinses, suggesting particles that were deeply embedded within the filter membrane as the result of shear-induced deagglomeration     

Flexible and Conductive 3D Printable Polyvinylidene Fluoride and Poly(N,N‐dimethylacrylamide) Based Gel Polymer Electrolytes

In this work, 3D printable gel polymer electrolytes (GPEs) based on N,N‐dimethylacrylamide (DMAAm) and polyvinylidene fluoride (PVDF) in lithium chloride containing ethylene glycol solution are synthesized and their physicochemical properties are investigated. 3D printing is carried out with a customized stereolithography type 3D gel printer named “Soft and Wet Intelligent Matter‐Easy Realizer” and free forming GPE samples having variable shapes and sizes are obtained. Printed PVDF/PDMAAm‐based GPEs exhibit tunable mechanical properties and favorable thermal stability. Electrochemical proprieties of the printed GPEs are carried out via impedance spectroscopy in the temperature range of 25–90 °C by varying PVDF content. Ionic conductivity as high as 6.5 × 10^?4 S cm^?1 is achieved at room temperature for GPE containing low PVDF content (5 wt%) and conductivity of the GPEs is increased as temperature rises.