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.

Microscopic Studies and Application of a Stabilized Ceric Ammonium Nitrate Oxidizer in Environmentally Friendly Pyrotechnic Strobes.

The growing reservations against the use of any kind of chlorine source in pyrotechnic items revolutionize the predominantly empirical development of strobe formulations in two ways. First, a conventionally applied ammonium perchlorate oxidizer needs to be replaced. Second, visible light emissions should no longer be generated by metastable monochloride species. Moreover, until now, toxic substances such as potassium dichromate have been added in order to achieve a more pronounced strobe effect. This work evaluates the potential of stearic acid-treated ceric ammonium nitrate to serve as an oxidizing agent in next-generation strobe compositions. For this purpose, its microscopic structure, energetic properties, and stability under ambient conditions were assessed. A two-component mixture with a magnesium-aluminum alloy was investigated, which should allow for the introduction of copper-based colorants. This potentially paves the way for the first environmentally friendly blue strobe formulations.

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.

Effects of intermittent feeding of tylosin phosphate during the finishing period on feedlot performance, carcass characteristics, antimicrobial resistance, and incidence and severity of liver abscesses in steers.

Liver abscesses (LA) are a source of economic loss for feedlot cattle feedlots, and the 2017 veterinary feed directive has restricted further use of tylosin phosphate to prevention and control of LA. Our objective was to evaluate effects of intermittent tylosin phosphate feeding on incidence and severity of LA in feedlot cattle and presence of total antimicrobial-resistant Enterococcus spp. Steers (n = 312, 411.4 ± 6.71 kg) were blocked by initial BW and randomly assigned to a treatment group. Treatments included a negative control group (no tylosin phosphate throughout the finishing period), a positive control group (tylosin phosphate fed continuously throughout the finishing period), and a group that received tylosin phosphate off-label by feeding the drug on a repeated intermittent basis (1 wk on, 2 wk off). Steers were housed in 24 soil-surfaced pens with 13 steers per pen. Body weights of cattle were obtained every 28 d and at the end of 119 d the steers were weighed and harvested at a commercial abattoir. Fecal samples were collected on days 0, 21, and 118 to characterize antimicrobial-resistant Enterococcus spp. Total LA percentage was greater (P = 0.012) for the no tylosin phosphate treatment compared with the other treatments, but did not differ between the continuous tylosin phosphate treatment and the intermittently fed tylosin phosphate treatment (P = 0.716). No difference was observed among treatments for ADG (P = 0.21), DMI (P = 0.28), or G:F (P = 0.75). Marbling score was lower (P = 0.022) for tylosin phosphate treatment when compared with both intermittent treatment and continuous tylosin phosphate treatment. Enterococcus spp. bacterial counts did not differ by treatment group over time (P > 0.05); however, there was a strong period effect for macrolide resistance among all groups (P < 0.01), suggesting an important environmental component as cattle were first placed in pens and then progressed through the feeding period. We conclude that feeding tylosin phosphate intermittently during the finishing phase decreases the total percentage of LA and maintains feedlot performance and carcass characteristics to the same extent as feeding tylosin phosphate throughout the finishing phase; furthermore, we hypothesize that enteric antimicrobial resistance is a result of longer term antibiotic usage in a particular environment rather than a direct short-term result of the treatment during any given feeding period.

Human galanin (GAL) and galanin 1 receptor (GALR1) variations are not involved in fat intake and early onset obesity.

The neuropeptide galanin (GAL) is involved in food intake and in fat ingestion. Presumably, these effects are conveyed via the galanin 1 receptor (GALR1). We screened the coding region of GAL (including 444 bp of its promoter region) and GALR1 for mutations using single-strand conformation polymorphism analysis and denaturing HPLC in up to 191 obese children and adolescents and 106 healthy underweight young adults (students). In GAL, we identified 3 novel single nucleotide polymorphisms (SNPs; silent: g.-419T-->C, g.-244G-->A; missense: g.47C-->T: Ala16Val) and one infrequent missense variation (c.253A-->G: Asn85Asp), and in GALR1 2 novel SNPs (silent: c.150C-->T, missense: c.793A-->T: Ile265Phe). To test for an association with obesity, we genotyped 7 SNPs (GAL: g.-244G-->A, g.47C-->T, rs7101947, rs1042577, rs3136540; GALR1: c.150C-->T, c.793A-->T) in up to 322 obese children and adolescents compared with up to 277 healthy underweight and normal weight young adults. Furthermore, we analyzed these SNPs with respect to potential effects on the percentage of energy consumed as fat in obese children and adolescents. Allele and genotype frequencies did not differ among the groups tested. In addition, we performed a pedigree transmission disequilibrium test (PDT) for one SNP (GAL: g.-244G-->A) in 610 (518 independent) obesity-trios (obese child or adolescent and both of its parents). However, the PDT for SNP GAL g.-244G-->A revealed no transmission disequilibrium. We conclude that the analyzed SNPs in GAL and GALR1 do not play a major role in early onset obesity or dietary fat intake in the obese children and adolescents of our study groups.