Radiological features of arterial channels in the equine third phalanx measured using a novel customized software represent changes of laminitis.

OBJECTIVE: To identify and measure radiolucencies at the solear margin of the distal phalanx in radiographs of healthy and laminitic hooves. SAMPLE: Clinical records and dorsoproximal-palmarodistal radiographs of equine forelimbs with radiological diagnoses of either laminitis (n = 40, L) or navicular syndrome (n = 40, NS). METHODS: Outlines of the radiolucent structures at the solar margin were drawn in ImageJ, and a customized novel plugin "Arteries Analyzer/ImageJ" was used for measurements. The diverging radiolucencies outside the terminal arc of the distal phalanx were differentiated as arterial channels (open at the solear margin) and ellipses (closed at the solear margin). Comparisons between L and NS, between distal phalanges with and without ellipses, and of arterial channels and ellipses in areas were compared using Wilcoxon and the Mann-Whitney U tests, respectively. The reliability and repeatability of the method were tested using Friedman's test. RESULTS: Fewer arterial channels but more ellipses were identified in L than in NS. In phalanges with ellipses (n = 47), the number of ellipses and the number of arterial channels were negatively correlated (PCC -0.181, P = .224). The number of ellipses correlated positively with the severity of laminitis (PCC 0.495, P < .001; n = 80) and with the degree of rotation of the distal phalanx (PCC 0.392, P < .001; n = 80). CLINICAL RELEVANCE: The software tool successfully measured arterial channels and ellipses outlined by the evaluators. Results indicate that healthy arteries develop into pathological ellipses in laminitic feet. This may be used to complement the interpretation of radiographs and support clinical decision-making.

Separation and identification of a complex flurbiprofen-polyethylene glycol mono- and diester mixture via a hyphenated HPLC-DAD-HRMS/SPE NMR system.

We report the use of a hyphenated HPLC-DAD(diode array detector)-HRMS/SPE NMR system for the separation and isolation of a complex mixture of esters, containing substances with very similar LC retention times. The literature known mono- and diesters of the drug Flurbiprofen and polyethylene glycol, which form a large number of substances with varying chain lengths, were chosen for this study. We demonstrate the use of this hyphenated system to quickly and effectively isolate sixteen of these highly similar individual esters in an automated fashion, demonstrating its applicability in standard pharmaceutical analysis and quality control of drugs. Both, synthetic solutions of these esters and extracts from Flurbiprofen lozenges were used for this purpose. By the sole use of this system, the individual compounds were isolated and UV, HRMS and 1D and 2D NMR data could be collected, enabling the identification and differentiation of the individual esters.

Isolation, Identification and Structural Verification of a Methylene-Bridged Naloxone "Dimer" Formed by Formaldehyde.

We report the isolation and characterization of a methylene bridged "dimer" of the opioid antagonist Naloxone, previously detected in experimental Buprenorphine-Naloxone oral films. This compound was found to form via an aldol addition followed by a condensation reaction under acidic conditions between two units of Naloxone and one unit of formaldehyde. HPLC-UV-HRMS analysis revealed the formation of three individual stereoisomers during this reaction, which were separately isolated using solid-phase extraction. These isomers were shown to freely react into one another in solvent, forming an equilibrium. The structure of the unknown compound was determined via HRMS spectrometry and 1D and 2D NMR spectroscopy.

Formation of a Thiol-Ene Addition Product of Asthma Medication Montelukast Caused by a Widespread Tin-Based Thermal Stabilizer.

We report the formation and characterization of two diastereomeric thiol-ene addition products of the asthma medication Montelukast within chewing tablets. Widespread tin-based thermal stabilizers dioctyltin bis(2-ethylhexyl thioglycolate) and monooctyltin tris(2-ethylhexyl thioglycolate), used in the manufacturing process of the medication's forming foil, were identified as the source of the thiol reactant, showing that these stabilizers may play a part in the degradation of Montelukast and APIs with functionalities similar to those of Montelukast, which should be considered during development of medication. The isolation and analysis of these impurities was performed by HPLC and UV-vis spectroscopy. HRMS and NMR data were collected to characterize and determine the structures of these compounds.

Development of a novel calorimetry setup based on metallic paramagnetic temperature sensors.

We have developed a new micro-fabricated platform for the measurement of the specific heat of low heat capacity mg-sized metallic samples, such as superconductors, down to temperatures of as low as 10 mK. It addresses challenging aspects of setups of this kind such as the thermal contact between the sample and platform, the thermometer resolution, and an addenda heat capacity exceeding that of the samples of interest (typically nJ/K at 20 mK). The setup allows us to use the relaxation method, where the thermal relaxation following a well defined heat pulse is monitored to extract the specific heat. The sample platform (5 × 5 mm2) includes a micro-structured paramagnetic Ag:Er temperature sensor, which is read out by a dc-superconducting quantum interference device via a superconducting flux transformer. In this way, a relative temperature precision of 30 nK/Hz can be reached, while the addenda heat capacity falls well below 0.5 nJ/K for T < 300 mK. A gold-coated mounting area (4.4 × 3 mm2) is included to improve the thermal contact between the sample and platform.