An ultra high-performance liquid chromatographic method was developed to study the cinitapride metabolism. Metabolites were generated from the incubation of cinitapride with human liver microsomes. Cinitapride and its metabolites were separated by reversed-phase mode using a formate aqueous solution (pH 6.5) and acetonitrile as the components of the mobile phase. Chromatographic conditions, including the establishment of an elution gradient, were optimized for obtaining the maximum number of resolved components in the minimum analysis time. Experimental design and multicriteria decision-making strategies were utilized to facilitate the optimization of chromatographic conditions. Figures of merit were evaluated with cinitapride standards and incubated samples. Limits of detection are about 0.03 μmol/L, and repeatabilities are better than 0.06% for retention times and better than 3.5% for concentrations. The method was applied to characterize the in vitro cinitapride metabolism with human liver microsomes. 相似文献
Endotoxins (also known as lipopolysaccharides (LPS)) are undesirable by products of recombinant proteins, purified from Escherichia coli. LPS can be considered stable under a wide range of temperature and pH, making their removal one of the most difficult tasks in downstream processes during protein purification. The inherent toxicity of LPS makes their removal an important step for the application of these proteins in several biological assays and for a safe parenteral administration. Immobilized metal affinity chromatography (IMAC) enables the affinity interactions between the metal ions (immobilized on the support through the chelating compound) and the target molecules, thus enabling high efficiency separation of the target molecules from other components present in a mixture. Affinity chromatography is applied with Ca2+ iminodiacetic acid (IDA) to remove most of the LPS contaminants from the end product (more than 90%). In this study, the adsorption of LPS on an IDA-Ca2+was investigated. The adsorption Freundlich isotherm of LPS-IDA-Ca2+provides a theoretical basis for LPS removal. It was found that LPS is bound mainly by interactions between the phosphate group in LPS and Ca2+ligands on the beads. The factors such as pH (4.0 or 5.5) and ionic strength (1.0 mol/L) are essential to obtain effective removal of LPS for contaminant levels between endotoxin’ concentration values less than 100 EU/mL and 100000 EU/mL. This new protocol represents a substantial advantage in time, effort, and production costs. 相似文献
Lolin, a new diterpene of the -clerodane type has been isolated from Teucrium capitatum. The X-ray structure and spectroscopic data of lolin is given. 相似文献
The biomimetic synthesis of the bisesquiterpene lactones (+/-)-biatractylolide 1 and (+/-)-biepiasterolide 2 via dimerization of the captodative stabilized radical 8 is reported. Atractylon 7 has also been shown to be a possible intermediate during the biosynthesis of biatractylolide 1, biepiasterolide 2, atractylolide 3, and hydroxyatractylolide 4. 相似文献
The total synthesis of the naturally occurring kinase inhibitor pyridovericin 1 is reported. A flexible and efficient synthesis has been accomplished in good yield from readily available 2,4-dihydroxypyridine. Pyridovericin is a key intermediate in our proposed biomimetic synthesis of pyridomacrolidin 2. 相似文献
We fabricate and characterize capsules that are composite membranes, made of a polymer network stabilized by adsorption to colloids and inflated by osmotic pressure from internal free polyelectrolyte; here, poly-l-lysine forms the network and inflates the capsules. To assess these capsules' properties and structure, we deform capsules using microcantilevers and use finite element modeling to describe these deformations. Additional experimental tests confirm the model's validity. These capsules' resilient response to mechanical forces indicates that loading and shear should be good triggers for the release of contents via deformation. The osmotic pressure inflating these capsules has the potential to trigger release of contents via deflation in response to changes in the capsules' environment; we demonstrate addition of salt as a trigger for deflating capsules. Because these capsules have a variety of release triggers available and the technique used to fabricate them is very flexible and allows high encapsulation efficiency, these capsules have very high potential for application in many areas. 相似文献
Cytarabine (1-β-d-arabinofuranosylcytosine, Ara-C), a pyrimidine nucleoside analogue, is used for the treatment of both acute and chronic myeloblastic leukemias and non-Hodgkin lymphoma. It has a very short plasma half-life and a very low oral bioavailability. To overcome these disadvantages, much effort has been focused on the design of cytarabine prodrugs. In this study, we have synthesized four different cytarabine prodrugs in order to increase the drug lipophilicity and the affinity of the prodrugs toward the biological membranes, as well as the lipophilic carriers. Differential scanning calorimetry was used to study the interaction of cytarabine and its prodrugs with multilamellar vesicles (MLVs) made of dimyristoylphosphatidylcholine (DMPC) and used as a model of biomembranes as well as a lipophilic carrier. The results showed that the 4-N-acetyl-2′,3′-5′-acetyl derivative and the prodrug with short chain fatty acids do not have a significant affinity with MLVs, whereas the prodrugs with long chain fatty acids have a stronger affinity with the MLVs with respect to cytarabine. The entity of the affinity depends on the fatty acids length. The increased affinity could be due to the fatty acid moieties which allow the molecule to insert among the phospholipid molecules. These results provide information on the interaction of these prodrugs with biomembranes and could be useful to design liposomes as carriers for the prodrugs.