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The aim of this study was to investigate the chiral inversion and the stereoselective pharmacokinetic profiles of desmethyl‐phencynonate hydrochloride after administration of the single isomer and its racemate to beagle dogs. A liquid chromatography with tandem mass spectrometry (LC–MS/MS) method was established for determination of the stereoisomers on chiral columns in beagle dog plasma, which met all the requirements. The chiral inversion in dogs of the desmethyl‐phencynonate hydrochloride were studied after administration of the single isomer or the racemic modification. The stereoselective pharmacokinetic profiles of the desmethyl‐phencynonate hydrochloride were studied by assays for simultaneous isomers after administration of the racemic modification. The results showed that the absorption of the R-configuration dosed as the single isomer was higher than it dosed as the racemic modification. The AUC(0‐t), AUC(0‐∞), and Cmax of the S-configuration were much higher than those of R-configuration after oral administration of the racemic desmethyl‐phencynonate hydrochloride. The chiral inversion of desmethyl‐phencynonate isomers could not occur in dogs after administration of the R-configuration. [ABSTRACT FROM AUTHOR]

As a major plant‐derived soil organic carbon (SOC) component, lignin phenols are unique biomarkers that reflect biogeochemical characteristics under different vegetation compositions and climatic zones in coastal wetlands. However, the latitudinal patterns of plant‐derived lignin phenols to SOC and their link with the stability and controlling mechanisms remain poorly understood.A total of 156 soil samples from 39 sites along a 5000 km coastal transect, were taken to explore the effects of biological and environmental controls on the patterns of lignin phenols. Lignin phenols had contents ranging from 1.91 to 83.3 mg g−1 OC, and a positive correlation was detected in grass‐dominated salt marsh, but a weakly negative correlation in mangrove. Positive correlations between SOC or lignin content and C/V or S/V (the cinnamyl‐ or syringyl‐to‐vanillyl) ratios were found, while overall negative correlations between SOC or lignin content and (Ad/Al)V or (Ad/Al)S (the acid‐to‐aldehyde of vanillyl or syringyl units) ratios were detected, respectively, which confirmed the validity of these lignin biomarker degradation parameters.Our findings revealed that plant C inputs and monomer ratios directly influenced the capacity of lignin phenols in soils. Lignin content and stabilization was mainly controlled by soil properties (i.e. pH, EC sand/clay). Mean annual temperature (MAT) influenced the patterns of lignin phenols both directly by increasing decomposition and indirectly by changing the vegetation and soil biogeochemistry (i.e. microbial substrate availability).Coastal wetlands are characterized by high primary productivity and C burial rate, yet plant‐derived lignin phenols are not as much as we thought compared to microbial residues C. Precise identification and quantification of the origin, decomposition, and determinants of lignin phenols help us understand their contribution to C sequestration and its response to climate and environmental changes. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

RATIONALE: Heparin and low molecular weight heparin (LMWH) are widely used as clinical anticoagulants. The determination of their composition and structural heterogeneity still challenges analysts. METHODS: Disaccharide compositional analysis, utilizing heparinase-catalyzed depolymerization, is one of the most important ways to evaluate the sequence, structural composition and quality of heparin and LMWH. Hydrophilic interaction chromatography coupled with quadruple time-of-flight mass spectrometry (HILIC/QTOFMS) has been developed to analyze the resulting digestion products. RESULTS: HILIC shows good resolution and excellent MS compatibility. Digestion products of heparin and LMWHs afforded up to 16 compounds that were separated using HILIC and analyzed semi-quantitatively. These included eight common disaccharides, two disaccharides derived from chain termini, three 3-O-sulfo-group-containing tetrasaccharides, along with three linkage region tetrasaccharides and their derivatives. Structures of these digestion products were confirmed by mass spectral analysis. The disaccharide compositions of a heparin, two batches of the LMWH, enoxaparin, and two batches of the LMWH, nadroparin, were compared. In addition to identifying disaccharides, 3-O-sulfo-group-containing tetrasaccharides, linkage region tetrasaccharides were observed having slightly different compositions and contents in these heparin products suggesting that they had been prepared using different starting materials or production processes. CONCLUSIONS: Thus, compositional analysis using HILIC/QTOFMS offers a unique insight into different heparin products. [ABSTRACT FROM AUTHOR]

ABSTRACT YQA-14 is a novel and selective dopamine D3 receptor antagonist, with potential for the treatment of drug addiction. However, earlier compounds in its structural class tend to have poor oral bioavailability. The objectives of this study were to characterize the preclinical absorption, distribution, metabolism and excretion (ADME) properties and pharmacokinetics (PK) of YQA-14, then to simulate the clinical PK of YQA-14 using a physiologically based pharmacokinetics (PBPK) model to assess the likelihood of developing YQA-14 as a clinical candidate. For human PK prediction, PBPK models were first built in preclinical species, rats and dogs, for validation purposes. The model was then modified by input of human in vitro ADME data obtained from in vitro studies. The study data showed that YQA-14 is a basic lipophilic compound, with rapid absorption ( Tmax ~ 1 h) in both rats and dogs. Liver microsomal clearances and in vivo clearances were moderate in rats and dogs consistent with the moderate bioavailability observed in both species. The PBPK models built for rats and dogs simulated the observed PK data well in both species. The PBPK model refined with human data predicted that YQA-14 would have a clearance of 8.0 ml/min/kg, a volume distribution of 1.7 l/kg and a bioavailability of 16.9%. These acceptable PK properties make YQA-14 an improved candidate for further research and development as a potential dopamine D3R antagonism for the treatment of drug addiction in the clinic. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]