HPLC analysis of in vivo intestinal absorption and oxidative metabolism of salicylic acid in the rat

In vivo absorption and oxidative metabolism of salicylic acid in rat small intestine was studied by luminal perfusion experiment. Perfusion through the lumen of proximal jejunum with isotonic medium containing 250 μm sodium salicylate was carried out. Absorption of salicylate was measured by a validated HPLC‐DAD method which was evaluated for a number of validation characteristics (specificity, repeatability and intermediate precision, limit of detection, limit of quantification, linearity and accuracy). The method was linear over the concentration range 0.5–50 μg/mL. After liquid–liquid extraction of the perfusion samples oxidative biotransformation of salicylate was also investigated by HPLC‐MS. The method was linear over the concentration range 0.25–5.0 μg/mL. Two hydroxylated metabolites of salicylic acid (2,5‐dihydroxybenzoic acid and 2,3‐dihydroxybenzoic acid) were detected and identified. The mean recovery of extraction was 72.4% for 2,3‐DHB, 72.5% for 2,5‐DHB and 50.1% for salicylic acid, respectively. The methods were successfully applied to investigate jejunal absorption and oxidative metabolism of sodium salicylate in experimental animals. The methods provide analytical background for further metabolic studies of salycilates under modified physiological conditions.     

In vivo and in vitro metabolism of aspirin eugenol ester in dog by liquid chromatography tandem mass spectrometry

Aspirin eugenol ester (AEE) is a promising drug candidate for treatment of inflammation, pain and fever and prevention of cardiovascular diseases with fewer side effects than its precursor, aspirin. Investigation into its metabolic process in target animal species will help to illustrate its mechanism of action and to establish its residual mark compound to formulate its dosage. Six beagle dogs were orally given a dose of 20 mg kg^?1 of AEE and one dog was used to prepare blank liver microsomes. Their liver microsomes were prepared for in vitro study and their plasma and urine were collected for in vivo metabolic analysis using liquid chromatography tandem mass spectrometry. In this study we identified 10 metabolites, M1, M2, M3, M4, M5 in phase I and M6, M7, M8, M9, M10 in phase II. Based on the metabolites of AEE, the pathways of AEE metabolism in dog were demonstrated. Copyright © 2014 John Wiley & Sons, Ltd.     

Metabolism of Pyrene and Chrysene in Epithelial Human Bronchial and Hamster Lung Cells

Abstract

The metabolism of pyrene and chrysene in epithelial human bronchial and in hamster lung cells has been studied and found to be very similar in both systems, although it differs from that observed in rat lung microsomes. Metabolite profiles have been analyzed by means of capillary GC and by GC/MS.     

Rapid analysis of Saposhnikovia divaricate decoction metabolism in rats by UHPLC–Q-TOFMS and multivariate statistical analysis

Saposhnikovia divaricata is a commonly used traditional Chinese medicine in treating various diseases such as pyrexia, rheumatism and headache. So far, there have been few reports on the metabolism of orally administered Saposhnikovia divaricate decoction (SDD), hindering further study on its bioactive components and their pharmacological characteristics. In the present study, ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC–Q-TOFMS) was used coupled with principal component analysis (PCA) and partial least squared discriminant analysis (PLS-DA) to rapidly discover and identify the metabolites of SDD. According to the result of PLS-DA, a total of 139 ions of interest including 87 positive ions and 52 negative ions were extracted as SDD-related xenobiotics in urine. Finally, 12 and 65 compounds were identified as absorbed parent components and metabolites of SDD, respectively. Among them, 40 new metabolites were reported for the first time. Our results suggested that hydrolysis, hydroxylation, glucuronidation and sulfation are the major metabolic pathways of chromones, while hydroxylation, hydrogenation and sulfation are the main metabolic pathways of coumarins. This study is the first to explore the absorption and metabolism of SDD using UHPLC–Q-TOFMS, with results providing a basis for further study of its pharmacokinetics and discovery of its bioactive components.     

Message Passing and Metabolism

Active inference is an increasingly prominent paradigm in theoretical biology. It frames the dynamics of living systems as if they were solving an inference problem. This rests upon their flow towards some (non-equilibrium) steady state—or equivalently, their maximisation of the Bayesian model evidence for an implicit probabilistic model. For many models, these self-evidencing dynamics manifest as messages passed among elements of a system. Such messages resemble synaptic communication at a neuronal network level but could also apply to other network structures. This paper attempts to apply the same formulation to biochemical networks. The chemical computation that occurs in regulation of metabolism relies upon sparse interactions between coupled reactions, where enzymes induce conditional dependencies between reactants. We will see that these reactions may be viewed as the movement of probability mass between alternative categorical states. When framed in this way, the master equations describing such systems can be reformulated in terms of their steady-state distribution. This distribution plays the role of a generative model, affording an inferential interpretation of the underlying biochemistry. Finally, we see that—in analogy with computational neurology and psychiatry—metabolic disorders may be characterized as false inference under aberrant prior beliefs.