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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]

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Although many studies have attempted to reconstruct millennial‐scale hurricane patterns using various proxy‐based methods, it is still unclear what the most effective proxies are to identify storm surge deposits in different environmental settings. This study quantitatively compares the application of grain‐size, loss‐on‐ignition, stable isotopes, X‐ray fluorescence, and palynological proxies in paleotempestology from an organic‐rich environment in the Florida Everglades. The nonparametric tests indicate that only 9 among the 27 parameters (mean diameter, %water, %organic, %carbonate, Ca, Sr, Ca/Ti, Cl/Br, and marine microfossils) exhibited significant differences between storm‐surge and in situ deposits. The principal component analysis shows that five marine indicators (Sr, Ca, Ca/Ti, %Carbonate, and Marine microfossils) have the closest association with the allochthonous samples, while Cl/Br and Mz are the most sensitive proxies in low‐ and high‐energy environments, respectively. Moreover, organic geochemical proxies (e.g., δ13C and δ15N of bulk sedimentary organic matter) are ineffective for identifying storm‐surge deposits in organic‐rich mangrove environments. Plain Language Summary: To help objectively identify the occurrence of storm‐surge deposits in coastal sediment cores, this study uses a statistical approach to evaluate the effectiveness of 27 widely used sedimentological, organic and inorganic geochemical, and biological parameters in distinguishing allochthonous deposits from autochthonous deposits in an organic‐rich environment in the Florida Everglades. The results show that Ca, Sr, Ca/Ti, and marine microfossil are four of the most sensitive parameters to distinguish storm‐surge deposits in organic‐rich environments in south Florida. In addition, Cl/Br can be used to indicate storm surge inundation in further inland and lower‐energy environments. Moreover, organic geochemical proxies cannot effectively distinguish storm‐surge deposits from in situ deposits in mangrove‐dominated coastal zones. Future studies need to explore the use of more specific organic geochemical proxies (e.g., biomarker) in mangrove‐dominated environments and evaluate the effective proxies in detecting storm deposits from sandy, deltaic/estuarine, and nontropical coastal environments. Key Points: Ca, Sr, Ca/Ti, and marine microfossil are the most sensitive parameters to identify storm‐surge deposits in organic‐rich environmentsCl/Br can be used to indicate storm surge inundation in further inland and lower energy environmentsOrganic geochemical proxies cannot effectively distinguish storm‐surge deposits from in situ deposits in mangrove‐dominated coastal zones [ABSTRACT FROM AUTHOR]

A 5.25‐m sediment core SRM‐1 and 45 surface samples from mangrove forests at the Shark River Estuary in the Everglades National Park, Florida, were examined by using X‐ray fluorescence and carbon isotopic analyses to study the history of intense hurricane landfall during the Late‐Holocene. Significance testing of the surface samples in relation to storm deposits from Hurricane Wilma suggests that elemental concentration of Sr and Cl and the ratio of Cl/Br are the most sensitive indicators for major hurricane events in our study area. The geochemical data sets of core SRM‐1 identified five active periods of intense hurricane activities during the last 3,500 years at ~3,400–3,000, ~2,200–1,500, ~1,000–800, ~600–300, and ~150 calibrated years before present to present. This is the longest paleohurricane record to date from South Florida. Our results are consistent with the view that intense hurricane activities in South Florida were modulated by Intertropical Convergence Zone (ITCZ) movements, El Niño/Southern Oscillation (ENSO) activities, and North Atlantic Oscillation (NAO) strength. This study contributes to the methodological advancement in paleotempestological studies by demonstrating that geochemical signals, particularly signals of saltwater intrusions, can be preserved in the sediment profiles on millennial time‐scale and measured by X‐ray fluorescence techniques, thereby enabling more storm records to be produced from otherwise suboptimal sand‐limited coastal systems such as the Florida Everglades. More work needs to be done to explore the use of geochemical and stable isotopic analyses in detecting storm signals from sand‐limited coastal environments. Plain Language Summary: This study uses geochemical analyses to detect intense hurricanes that made landfall near the southwest coast of the Florida Everglades from sediment profiles. The geochemical data sets identified five active periods of intense hurricane activities during the last 3,500 years at ~3,400–3,000, ~2,200–1,500, ~1,000–800, ~600–300, and ~150 years ago. Results from this study agree with previous studies that intense hurricane activities in the western Atlantic Basin were controlled by the position of ITCZ, ENSO activities, and NAO strength. Key Points: This study demonstrates the use of XRF analysis in detecting major hurricane events in sand‐limited coastal systemsFive active hurricane periods were identified at ~3,400–3,000, ~2,200–1,500, ~1,000–800, ~600–300, and ~150 cal yr BP to presentThis study suggests that intense hurricane activities in the western Atlantic Basin were modulated by ITCZ, ENSO, and NAO activities [ABSTRACT FROM AUTHOR]

In this paper, grain‐size records of 128 surface samples and six sediment cores retrieved from freshwater marshes across the Sanjiang Plain were employed to reconstruct the marshes' hydrological variation during the Holocene and to discuss its links to the East Asian summer monsoon (EASM) variation. The grain‐size hydrological significance for the marshes' deposits was first interpreted by quantitative analyses of 128 modern samples. The results indicate that the sand fraction exhibits a higher level significance to modern water‐level conditions than other grain‐size parameters. Thus, the sand accumulation rates of the six cores were calculated and employed to reconstruct the Holocene hydrological regime of the marshes on the plain. Based on the cluster analysis, it can be identified that three higher water‐level stages occurred during 6.2–5.6 thousand yr BP, 5.6–4.5 thousand yr BP, and 2.8–2.4 thousand yr BP, whereas four lower water‐level stages occurred during ~8.0–6.2 thousand yr BP, 4.5–2.8 thousand yr BP, 2.4–0.7 thousand yr BP, and 0.7–0 thousand yr BP, respectively. Considering the prevalent monsoon climate on the modern Sanjiang Plain, it is reasonable to believe that the local water‐level fluctuations were mainly regulated by the EASM variation rather than local factors including flooding, waterway modification, depression infilling, and human activities. The higher water‐level stages were linked to a stronger EASM and vice versa. This study provides essential background datasets for understanding the potential controls on the marsh development and degradation on the Sanjiang Plain. [ABSTRACT FROM AUTHOR]

A rapid, specific and high-throughput stable isotope-dilution LC-MS/MS method was developed and validated with high sensitivity for the quantification of R-phencynonate (a eutomer of phencynonate racemate) in rat and dog plasma. Plasma samples were deproteinized using acetonitrile and then separated on a C8 column with an isocratic mobile phase containing acetonitrile-water-formic acid mixture (60:40:0.1, v/v/v) at a flow rate of 0.2 mL/min. Each sample had a total run time of 3 min. Quantification was performed using triple quadrupole mass spectrometry in selected reaction monitoring mode with positive electrospray ionization. The method was shown to be highly linear ( r2 > 0.99) and to have a wide dynamic range (0.1-100 ng/mL) with favourable accuracy and precision. No matrix effects were observed. The detailed pharmacokinetic profiles of R-phencynonate at therapeutic doses in rats and dogs were characterized by rapid oral absorption, quick clearance, high volume of distribution and poor absolute bioavailability. R-Phencynonate lacked dose proportionality over the oral dose range, based on the power model. However, the area under concentration-time curve and the maximum plasma concentration increased linearly in a dose-dependent manner in both animal models. The absolute bioavailability of R-phencynonate was 16.6 ± 2.75 and 4.78 ± 1.26% in dogs and rats, respectively. [ABSTRACT FROM AUTHOR]

The herb-derived compounds silymarin, glycyrrhizin, and oxymatrine are widely used to treat chronic hepatitis C virus infections in China. They are often prescribed in combination with ribavirin, which has a narrow therapeutic index. We investigated the influence of these compounds on ribavirin pharmacokinetics following concurrent administration at the human dose in rats. Pharmacokinetic parameters were determined in rats following oral (p.o.) administration of ribavirin (30 mg/kg) with or without silymarin (40 mg/kg, p.o.), glycyrrhizin (15 mg/kg, intraperitoneal [i.p.]), or oxymatrine (60 mg/kg, p.o.). Compared with the animals in ribavirin group, silymarin significantly decreased the area under the plasma concentration-time curve (AUC0-t ) and the peak plasma concentration (Cmax ) of ribavirin and ribavirin base by 31.2-44.5% and 48.9-50.0%, respectively. Glycyrrhizin significantly decreased the Cmax and AUC0-t of both ribavirin and its metabolite by 35.3-37.6% and 38.6-39.8%, respectively. However, silymarin or glycyrrhizin did not change the ribavirin metabolite/parent ratios of the AUC and Cmax . Oxymatrine did not induce significant changes in ribavirin concentration, but it significantly decreased the Cmax (26.6%) and AUC (21.8%) of the metabolite. This study indicates that the therapeutic efficacy of ribavirin may be compromised by the concurrent administration of herbal medicines/dietary supplements containing silymarin, glycyrrhizin, or oxymatrine. [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]