Development and validation of a stability-indicating ultra-high-performance liquid chromatography method for the estimation of ibrutinib and trace-level quantification of related substances using quality-by-design approach

A new ultra-high-performance liquid chromatography method was developed using quality-by-design principles for quantifying trace-level impurities of ibrutinib. The method utilized an ACQUITY UPLC BEH C18 column with a mobile phase consisting of equal parts of 0.02 M formic acid in water and 0.02 M formic acid in acetonitrile. The critical method parameters, including mobile phase pH, column temperature, and flow rate, were optimized using the design of experiments. Statistical analysis revealed the impact of these parameters on critical quality attributes. Perturbation and response surface plots illustrated the individual and interactive effects of the parameters. The optimal parameter levels were determined to be pH, 2.5; column temperature, 28°C; and flow rate, 0.55 mL/min. Confirmation experiments demonstrated the method's robustness, with the separation of impurities and unknown degradation products within a 5-min runtime. The optimized ultra-performance liquid chromatography method was validated according to ICH guidelines. The method exhibited linear response within the range of 0.025–100 μg/mL for ibrutinib and 0.0187–0.225 μg/mL for impurities (r² > 0.9995), with limits of detection/limits of quantification of 0.01/0.025 and 0.015/0.0187 for ibrutinib and four impurities, respectively. Recoveries for the drug and impurities ranged from 92.69 to 102.7%, and precision was below 2% and 8% relative standard deviation for ibrutinib and impurities, respectively.     

Hydrogen bonding and halogen bonding co-existing in the reaction of heptafluorobenzyl iodide with N,N,N,N-tetramethylethylene diamine

Two novel assembling systems 3 and 4, with the structures of C₆F₅CF₂⁻?H⁺N(Me)₂CH₂CH₂(Me₂)N⁺H?⁻CF₂C₆F₅ and C₆F₅CF₂I?N(Me)₂CH₂CH₂(Me)₂N?ICF₂C₆F₅, respectively, have been generated from the solution of heptafluorobenzyl iodide 1 and N,N,N^′,N^′-tetramethylethylenediamine 2 in dichloromethane. Their structures have been characterized by X-ray diffraction analysis, NMR and IR spectroscopy. Intermolecular N?I halogen bond and F?H hydrogen bond are revealed to be the driving forces for their formation.     

Preparation of β-cyclodextrin sulfate-immobilized hydrophilic vinyl-polymer gel as a selective,high recovery and stable adsorbent for high-performance affinity chromatography of heparin-binding substances

Summary β-Cyclodextrin sulfate having heparin-mimicking activity was immobilized on a hydrophilic vinyl-polymer gel, TSKgel AF-Epoxy, TOYOPEARL 650M. A column packed with this material could be used for high-performance affinity chromatographic separation of heparin-binding substances such as growth factors, enzymes, coagulation factors and lipoproteins. The substances retained on the column were recovered more easily than those on a heparin-immobilized column. Furthermore, the β-Cyclodextin sulfate-immobilized gel was superior in stability to the heparin-immobilized gel when exposed to acidic and basic solutions.     

Volatile flavoring substances in foodstuffs

The odor of most foods is produced by mixtures of many volatile flavoring substances. Over the past century, numerous food flavors have been analyzed in sufficient detail to allow a survey of the classes of substances responsible, the formation of individual flavoring substances, and their fixation in the foods. In addition to special biosynthetic pathways, the breakdown of fats and the Maillard reaction have been found to be particularly important to the formation of flavoring substances.     

Degradation pathways of dissolved carbon in landfill leachate traced with compound-specific 13C analysis of DOC

The isotopic compositions of carbon compounds in landfill leachate provide insights into the biodegradation pathways that dominate the different stages of waste decomposition. In this study, the carbon geochemistry of different carbon pools, environmental stable isotopes and compound-specific isotope analysis (CSIA) of leachate dissolved organic carbon (DOC) fractions and gases show distinctions in leachate biogeochemistry and methane production between the young area of active waste emplacement and the old area of historical emplacement at the Trail Road Landfill (TRL).

The active area leachate has low DOC concentrations (<200 mg l^?1) dominated by fulvic acid (FA=160 mg l^?1), and produces CH₄ dominantly by CO₂ reduction (D? excess=20.6‰). Leachate generated in the area of older waste has high DOC (>4770 mg l^?1) dominated by FA (4482 mg l^?1) and simple fatty acids (acetic=1008 mg l^?1 and propionic=608 mg l^?1), and produces CH₄ by the acetate fermentation pathway (D? excess=9.8‰). CSIA shows an advanced degradation and a progressive accumulation of ¹³C of fatty acids in leachate from the older area. The enriched ¹³C value of FA (?20 and?26‰ for the older and active parts, respectively,) and of low molecular weight DOC (?8 and?27‰) as well as of the bulk DOC (?21 and?25‰) shows more advanced degradation in the older part of the landfill, which is consistent with the shift in the humic/FA ratios (0.05 and 0.18). The ¹³C enrichment of acetate (?12‰) above the ¹³C of DOC (?21‰) and of propionic acid (?19‰), in older leachate, suggests that this acetate has not evolved from the simple degradation of larger organic molecules, but by homoacetogenesis from the enriched dissolved inorganic carbon (DIC) pool (8‰) and H_2, which produce a more enriched ¹³C of acetate. In contrast, the ¹³C of the minor acetate in the active area (?17‰) indicates that CO₂-reducing bacteria must be the primary consumers of H₂, which has resulted in enriched ¹³C_DIC (10‰) and depleted ¹³C_CH4 (?58‰).     

Vibrational Spectroscopy of Phenols and Phenolic Polymers. Theory,Experiment, and Applications

In the first part of this review, the authors give a survey on the literature of vibrational spectroscopy of phenol, phenol derivatives, and other phenolic componds from the last decade of the last century through today. The classical and modern methods of vibrational spectroscopy are also introduced and a glossary is included to aid comprehension. The second part deals with the literature regarding the importance of vibrational spectroscopy in the investigation and identification of phenolic compounds in natural substances, the application of vibrational spectroscopy in composite and synthetic polymer chemistry, and following of chemical processes and investigating their resulting products. Vibrational spectroscopy is a very good tool for determination of molecular structures and is important in chemical analysis and in the chemical industry.     

Histochemical and Phytochemical Analysis of Lamium album subsp. album L. Corolla: Essential Oil,Triterpenes, and Iridoids

The aim of this study was to conduct a histochemical analysis to localize lipids, terpenes, essential oil, and iridoids in the trichomes of the L. album subsp. album corolla. Morphometric examinations of individual trichome types were performed. Light and scanning electron microscopy techniques were used to show the micromorphology and localization of lipophilic compounds and iridoids in secretory trichomes with the use of histochemical tests. Additionally, the content of essential oil and its components were determined using gas chromatography-mass spectrometry (GC-MS). Qualitative analyses of triterpenes carried out using high-performance thin-layer chromatography (HPTLC) coupled with densitometric detection, and the iridoid content expressed as aucubin was examined with spectrophotometric techniques. We showed the presence of iridoids and different lipophilic compounds in papillae and glandular and non-glandular trichomes. On average, the flowers of L. album subsp. album yielded 0.04 mL/kg of essential oil, which was dominated by aldehydes, sesquiterpenes, and alkanes. The extract of the L. album subsp. album corolla contained 1.5 × 10⁻³ ± 4.3 × 10⁻⁴ mg/mL of iridoid aucubin and three triterpenes: oleanolic acid, β-amyrin, and β-amyrin acetate. Aucubin and β-amyrin acetate were detected for the first time. We suggest the use of L. album subsp. album flowers as supplements in human nutrition.     

FTO – an Electrode Material for the Stable Electrochemical Determination of Dopamine

Dopamine and other catecholamines play a keyrole for the interaction of numerous processes in the neuronal network. Hence, numerous detection methods have been developed. Electrochemical sensor developments for catecholamines are characterized mostly by complex modification strategies in order to avoid a disturbance of the sensor signal by interfering substances. Here the application of fluorine doped tin oxide (FTO) as electrode material for dopamine detection is reported avoiding the necessity of expensive modifications and stability problems. This FTO based electrode allows the discrimination between dopamine and its precursor as well as its methylated degradation product and is not disturbed by typical interfering compounds (ascorbic acid, uric acid) and is characterized by high linearity and stability of the sensor signal for repeated measurements.     

Nonmetallic Wurtz coupling reaction of perfluorohexyl iodide

It is shown for the first time that the Wurtz reaction can be realized by the action of an organic substance (triphenylphosphine) on an alkyl halide (perfluoroalkyl iodide) without the use of metals. It was found that when trying to prepare the bis(3,3′-aminophenyl)(fluoroalkyl)phosphine oxide by four-step synthesis, in the first stage of the reaction of perfluoro-1-iodohexane with triphenylphosphine does not proceed towards the formation of an intermediate quaternary phosphonium salt. Instead, the carbon chain of perfluoroalkyl iodide dimerizes to form perfluorododecane – Wurtz reaction product. We have proposed a new pathway for homocoupling of perfluoroalkylhalides into even-numbered perfluoroalkanes.