The 8th GCC Closed Forum for Bioanalysis was held in Baltimore, MD, USA on 5 December 2013, immediately following the 2013 AAPS Workshop (Crystal City V): Quantitative Bioanalytical Methods Validation and Implementation--The 2013 Revised FDA Guidance. This GCC meeting was organized to discuss the contents of the draft revised FDA Guidance on bioanalytical method validation that was published in September 2013 and consolidate the feedback of the GCC members. In attendance were 63 senior-level participants, from seven countries, representing 46 bioanalytical CRO companies/sites. This event represented a unique opportunity for CRO bioanalytical experts to share their opinions and concerns regarding the draft FDA Guidance, and to build unified comments to be provided to the FDA.
BackgroundIn the United States, hemodialysis (HD) is generally performed via a bicarbonate dialysate. It is not known if small amounts of acid used in dialysate to buffer the bicarbonate can meaningfully contribute to overall buffering administered during HD. We aimed to investigate the metabolism of acetate with use of two different acid buffer concentrates and determine if it effects blood bicarbonate concentrations in HD patients.MethodsThe Acid-Base Composition with use of hemoDialysates (ABChD) trial was a Phase IV, prospective, single blind, randomized, cross-over, 2 week investigation of peridialytic dynamics of acetate and bicarbonate associated with use of acid buffer concentrates. Eleven prevalent HD patients participated from November 2014 to February 2015. Patients received two HD treatments, with NaturaLyte® and GranuFlo® acid concentrates containing 4 and 8 mEq/L of acetate, respectively. Dialysate order was chosen in a random fashion. The endpoint was to characterize the dynamics of acetate received and metabolized during hemodialysis, and how it effects overall bicarbonate concentrations in the blood and dialysate. Acetate and bicarbonate concentrations were assessed before, at 8 time points during, and 6 time points after the completion of HD.ResultsData from 20 HD treatments for 11 patients (10 NaturaLyte® and 10 GranuFlo®) was analyzed. Cumulative trajectories of arterialized acetate were unique between NaturaLyte® and GranuFlo® (p = 0.003), yet individual time points demonstrated overlap without remarkable differences. Arterialized and venous blood bicarbonate concentrations were similar at HD initiation, but by 240 min into dialysis, mean arterialized bicarbonate concentrations were 30.2 (SD ± 4.16) mEq/L in GranuFlo® and 28.8 (SD ± 4.26) mEq/L in NaturaLyte®. Regardless of acid buffer concentrate, arterial blood bicarbonate was primarily dictated by the prescribed bicarbonate level. Subjects tolerated HD with both acid buffer concentrates without experiencing any related adverse events.ConclusionsA small fraction of acetate was delivered to HD patients with use of NaturaLyte® and GranuFlo® acid buffers; the majority of acetate received was observed to be rapidly metabolized and cleared from the circulation. Blood bicarbonate concentrations appear to be determined mainly by the prescribed concentration of bicarbonate.Trial registrationThis trial was registered on ClinicalTrials.gov on 11 Dec 2014 (NCT02334267).Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-017-0683-6) contains supplementary material, which is available to authorized users.
Ionic conductors are solids that have a large number of defects and easy pathways that make it possible for ions to move over long distances in an electric field. In order to be mobile an ion must be small and have a low charge. The fluoride ion is the most mobile anion. The highest performance fluoride ion conductors contain divalent tin, and have a highly layered crystal structure related to the CaF 2 fluorite type. BaSnF 4 has the α-PbSnF 4 structure, which is a √2/2×√2/2×2 superstructure of the fluorite type, where the tetragonal unit-cell and the value of the a and b parameters being equal to half the diagonals of the (a,b) face of fluorite are due to the loss of the F Bravais lattice, and the Sn Sn Ba Ba order along the c parameter is at the origin of the doubling of the c parameter. The BaSnF 4 material was prepared first by Dénès et al. (C. R. Acad. Paris C, 280: 831, 1975), and its superionic properties were characterized by Dénès et al. (Solid State Ion., 13: 213, 1984). It was found to have a conductivity three orders of magnitude higher than that of BaF 2 , with an ionic conduction rate τ i >0.99. No BaSnF 4 was obtained by the aqueous medium, when aqueous solutions of SnF 2 and Ba(NO 3 ) 2 are mixed together; BaSn 2 F 6 was obtained instead. In a new development of this work, BaSnF 4 has been obtained by the wet method for the first time. X-ray powder diffraction showed that the BaSnF 4 phase obtained by the wet method varies substantially from one sample to another: (a) signification variations of the c parameter of the tetragonal unit-cell reveals that the interlayer distance is sensitive to the leaching conditions, possibly because some of the leached ions remain in the interlayer spacing; (b) large variations of the crystallite dimensions and, as a result of the twodimensionality of the structure, a strong crystallite dimension anisotropy are observed, with d∥
A flow-injection biosensor-like system based on a nonenzymatic approach has been developed to determine the carbamate pesticide carbaryl in complex biological samples without lengthy and expensive extraction steps. Molecularly imprinted polymeric beads were used to immobilize carbaryl from biological samples. pH variation permitted the elution of carbaryl from the binding cavity to the flow cell. A pH electrode was used to detect changes in the charge of carbaryl in the sample solution resulting from the protonation and deprotonation of the molecule over different pH ranges. At pH 2.0, the secondary amine group is protonated, giving a (+1) charge to the carbaryl molecule. At pH 8.0, the ionized carbaryl loses a proton to become neutral, changing the local pH of the flow cell. The pH change at the flow cell generated by the deprotonation of carbaryl ion in alkaline medium was used to determine the carbaryl concentration. Parameters influencing the performance of the system were optimized for use in the detection procedure. The validated biosensor-like system had a carbaryl detection limit of 10.0 microg/mL and a response that was linear (r2>0.98) over the concentration range of 10.0-00 microg/mL.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.