Metabolism of [(1)(4)C]prometryn in rats.

[(1)(4)C]Prometryn, 2, 4-bis(isopropylamino)-6-(methylthio)-s-triazine, was orally administered to male and female rats at approximately 0.5 and 500 mg/kg; daily urine and feces were collected. After 3 or 7 days rats were sacrificed, and blood and selected tissues were isolated. The urine and feces extracts were characterized for metabolite similarity as well as for metabolite identification. Over 30 metabolites were observed, and of these, 28 were identified mostly by mass spectrometry and/or cochromatography with available reference standards. The metabolism of prometryn was shown to occur by N-demethylation, S-oxidation, S-S dimerization, OH substitution for NH(2) and SCH(3), and conjugation with glutathione or glucuronic acid. Rat liver microsomal incubations of prometryn were conducted and compared to the in vivo metabolism. Both in vivo and in vitro phase I metabolisms of prometryn were similar, with S-oxidation and N-dealkylation predominating. The involvement of cytochrome P-450 and flavin-containing monooxidase in the in vitro metabolism of prometryn was investigated.     

Characterisation of tramadol,morphine and tapentadol in an acute pain model in Beagle dogs

ObjectiveTo evaluate the analgesic potential of the centrally acting analgesics tramadol, morphine and the novel analgesic tapentadol in a pre-clinical research model of acute nociceptive pain, the tail-flick model in dogs.Study designProspective part-randomized pre-clinical research trial.AnimalsFifteen male Beagle dogs (HsdCpb:DOBE), aged 12–15 months.MethodsOn different occasions separated by at least 1 week, dogs received intravenous (IV) administrations of tramadol (6.81, 10.0 mg kg^?1), tapentadol (2.15, 4.64, 6.81 mg kg^?1) or morphine (0.464, 0.681, 1.0 mg kg^?1) with subsequent measurement of tail withdrawal latencies from a thermal stimulus (for each treatment n = 5). Blood samples were collected immediately after the pharmacodynamic measurements of tramadol to determine pharmacokinetics and the active metabolite O-demethyltramadol (M1).ResultsTapentadol and morphine induced dose-dependent antinociception with ED50-values of 4.3 mg kg^?1 and 0.71 mg kg^?1, respectively. In contrast, tramadol did not induce antinociception at any dose tested. Measurements of the serum levels of tramadol and the M1 metabolite revealed only marginal amounts of the M1 metabolite, which explains the absence of the antinociptive effect of tramadol in this experimental pain model in dogs.Conclusions and clinical relevanceDifferent breeds of dogs might not or only poorly respond to treatment with tramadol due to low metabolism of the drug. Tapentadol and morphine which act directly on μ-opioid receptors without the need for metabolic activation are demonstrated to induce potent antinociception in the experimental model used and should also provide a reliable pain management in the clinical situation. The non-opioid mechanisms of tramadol do not provide antinociception in this experimental setting. This contrasts to many clinical situations described in the literature, where tramadol appears to provide useful analgesia in dogs for post-operative pain relief and in more chronically pain states.     

Quantification of the Robusta fraction in a coffee blend via Raman spectroscopy: proof of principle

Among the 100 different known Coffea species, Coffea arabica L. (Arabica) and Coffea canephora Pierre (Robusta) are the only two of commercial interest. They differ in a range of agronomic, genetic, and chemical properties. Due to the significant price difference between Arabica and Robusta, there is an economic incentive to illicitly replace Arabica with Robusta. Therefore, it is crucial to have accurate methods to determine the Robusta-to-Arabica-ratio in blends. This paper presents the proof of principle of a new and fast approach to determine the Robusta fraction in a blend based on Raman spectroscopy. The oils of two references (a pure Robusta and pure Arabica coffee) and six blends thereof consisting of different Robusta and Arabica fractions were extracted using a Soxhlet system. The solutes were analyzed by means of Raman spectroscopy without further workup. Using the intensity ratio between two Raman peaks, one characteristic for kahweol and one characteristic for fatty acids, allowed determinination of the Robusta content in a given mixture. The intensity ratio is linearly dependent on the Robusta content of the compound. Above a Robusta content of 75 wt %, kahweol was not detectable. The Raman data are in agreement with results obtained from the very time-consuming multistep DIN 10777 procedures based on HPLC.     

Clustering of temporal profiles using a Bayesian logistic mixture model: Analyzing groundwater level data to understand the characteristics of urban groundwater recharge

The hydrogeologic conditions of groundwater can be examined by carefully studying the patterns of fluctuations in groundwater levels. These fluctuations are spatially and temporally influenced by many complicated factors, including rainfall, topography, land use, and hydraulic properties of soils and bedrock (i.e., aquifers). In this article we report a methodology based on the Bayesian logistic mixture model to simultaneously cluster profiles of groundwater level changes over time and estimate the relationships between the characteristics of each cluster and environmental variables. We apply the proposed method to analyze groundwater level profiles from 37 monitoring wells in Seoul, South Korea, and we find four clusters of wells. Using the estimated relationship between the clusters and the environmental variables, we discern the hydrogeologic conditions of each cluster, thus gaining insight into the recharge and subsurface flow of bedrock groundwater in an urban setting and the vulnerability of groundwater to the inflow of potential pollutants from ground surface. This article has supplementary material online.