Comparative pharmacokinetics of verapamil and norverapamil in normal and ulcerative colitis rats after oral administration of low and high dose verapamil by UPLC-MS/MS.

In this study, UC rat model was established by administration of 5% (w/v) dextran sulfate sodium, and the pharmacokinetics of verapamil and norverapamil were evaluated in normal and UC rats using UPLC-MS/MS after oral administration of 5 mg/kg and 50 mg/kg verapamil.The peak concentration (Cmax) and the area under plasma concentration-time curves (AUC) of verapamil in UC rats after oral administration of 5 mg/kg were significantly greater (2.5 times and 2 times, respectively) than those in normal rats, but the clearance rate (Cl) was significantly lower (by 50%). For norverapamil, Cmax and AUC were significantly greater (2.8 times and 2.5 times, respectively), and Cl was significantly lower (by 45%). But, pharmacokinetic parameters of verapamil and norverapamil after oral administration of 50 mg/kg were no significant differences between UC and normal rats.The better absorption and poor excretion for low-dose verapamil may be attributed to down-regulation of P-gp expression in the intestine and kidney. No significant differences of pharmacokinetic parameters for high-dose verapamil may be explained as the saturation of an efflux mechanism.The findings of this study suggested that in UC patients, doses of verapamil should be decreased when low-dose verapamil was orally administrated.

Molecularly imprinted polymer solid-phase microextraction coupled with ultra high performance liquid chromatography and tandem mass spectrometry for rapid analysis of pyrrolizidine alkaloids in herbal medicine.

Pyrrolizidine alkaloids are the most widely distributed natural toxins, and pyrrolizidine alkaloid-containing herbal medicines are probably the most common poisonous plants affecting humans. We reported pyrrolizidine alkaloid-molecularly imprinted polymer solid-phase microextraction for the selective adsorption of toxic pyrrolizidine alkaloids from herbal medicine. A sulfonic compound, sodium allylsulfonate, was chosen as the functional monomer to interact with pyrrolizidine alkaloids through strong ionic interaction. To avoid template leakage and for the aim of cost saving, a relatively cheap dummy template was used for the fabrication of molecularly imprinted polymer-solid-phase microextraction fibers. The obtained fibers showed selective adsorption ability for four pyrrolizidine alkaloids, including europine, echimidine, lasiocarpine, and heliotrine. The extraction parameters, such as extraction time, extraction temperature, shaking speed, elution solvent and elution time, were optimized. Then ultra high performance liquid chromatography with mass spectrometry coupled with molecularly imprinted polymer-solid-phase microextraction method was developed for the fast and efficient analysis of four pyrrolizidine alkaloids from the model herbal plant Farfarae Flos. The established method was validated and exhibited satisfactory accuracy and precision. The present method provides an innovative and fast analytical strategy for the determination of trace toxic pyrrolizidine alkaloids in complicated samples.

Enrichment of total steroidal saponins from the extracts of Trillium tschonoskii Maxim by macroporous resin and the simultaneous determination of eight steroidal saponins in the final product by HPLC.

An effective and simple method was established for the separation and enrichment of steroidal saponins from Trillium tschonoskii Maxim. The adsorption and desorption properties of seven macroporous resins were investigated. Among the tested resins, AB-8 resin showed the best adsorption and desorption capacities. The adsorption of steroidal saponins on AB-8 at 25°C was quite consistent with both the Freundlich isotherm model and the pseudo-second-order kinetics model. By optimizing the dynamic adsorption and desorption parameters, the content of steroidal saponins increased from 5.20% in the crude extracts to 51.93% in the final product, with a recovery yield of 86.67%. Furthermore, by scale-up separation, the concentration and recovery of total steroidal saponins were 43.8 and 85.5%, respectively, which suggested that AB-8 resin had great industrial and pharmaceutical potential because of its high efficiency and cost-effectiveness. In addition, a high-performance liquid chromatography method for the simultaneous determination of eight steroidal saponins was established for the first time, which was employed to qualitatively and quantitatively analyze the final product. Based on the methodological validation results, the high-performance liquid chromatography method can be widely applied to the quality control of steroidal saponins from Trillium tschonoskii Maxim due to its excellent accuracy, stability, and repeatability.

Coamorphous Loratadine-Citric Acid System with Enhanced Physical Stability and Bioavailability.

Coamorphous systems using citric acid as a small molecular excipient were studied for improving physical stability and bioavailability of loratadine, a BCS class II drug with low water solubility and high permeability. Coamorphous loratadine-citric acid systems were prepared by solvent evaporation technique and characterized by differential scanning calorimetry, X-ray powder diffraction, and Fourier transform infrared spectroscopy. Solid-state analysis proofed that coamorphous loratadine-citric acid system (1:1) was amorphous and homogeneous, had a higher T g over amorphous loratadine, and the intermolecular hydrogen bond interactions between loratadine and citric acid exist. The solubility and dissolution of coamorphous loratadine-citric acid system (1:1) were found to be significantly greater than those of crystalline and amorphous form. The pharmacokinetic study in rats proved that coamorphous loratadine-citric acid system (1:1) could significantly improve absorption and bioavailability of loratadine. Coamorphous loratadine-citric acid system (1:1) showed excellently physical stability over a period of 3 months at 25°C under 0% RH and 25°C under 60% RH conditions. The improved stability of coamorphous loratadine-citric acid system (1:1) could be related to an elevated T g over amorphous form and the intermolecular hydrogen bond interactions between loratadine and citric acid. These studies demonstrate that the developed coamorphous loratadine-citric acid system might be a promising oral formulation for improving solubility and bioavailability of loratadine.

Preparation and evaluation of a molecularly imprinted sol-gel material as the solid-phase extraction adsorbents for the specific recognition of cloxacilloic acid in cloxacillin.

Highly selective molecularly imprinted polymers on the surface of silica gels were prepared by a sol-gel process and used as solid-phase extraction adsorbents for the specific recognition, enrichment and detection of cloxacilloic acid in cloxacillin. The obtained polymers were characterized by scanning electron microscopy, FTIR spectroscopy, nitrogen adsorption and desorption, elemental analysis and thermogravimetric analysis. The imprinted polymers not only possessed high adsorption capacity (6.5 µg/mg), but also exhibited fast adsorption kinetics (they adsorb 80% of the maximum amount within 20 min) and excellent selectivity (the imprinted factor was 3.6). A method using the imprinted polymers as solid-phase extraction adsorbents coupled with high-performance liquid chromatography was established with good specificity, linearity (r = 0.9962), precision (ranging from 0.5 to 6.7%), accuracy (ranging from 93.9 to 97.7%) and extraction recoveries (ranging from 78.8 to 89.8%). The limits of detection and quantification were 0.07 and 0.25 mg/g, respectively. This work could provide a promising method in the enrichment, extraction and detection of allergenic impurities in the manufacture, storage and application of cloxacillin.

An HPLC method for the determination of a novel anti-hypertension agent 6,7-dimethoxy-3-(4-(4-fluorobenzyloxy)-3-methoxyphenylmethyl)quinazolin-4(3H)-one in rat plasma: application to pharmacokinetic study.

6,7-dimethoxy-3-(4-(4-fluorobenzyloxy)-3-methoxyphenylmethyl) quinazolin-4(3H)-one (DFMQ-19), a novel analogue of 3-benzylquinazolin-4(3H)-ones, may be considered as a drug candidate for the treatment of hypertension. The aim of this study was to develop and validate a reverse-phase high-performance liquid chromatography to determine the DFMQ-19 in plasma and demonstrate its application in pharmacokinetic study. Separation of DFMQ-19 and I.S (structural analog of DFMQ-19) was performed using Shim-Pack VP-ODS column and a mixture of acetonitrile and water as mobile phase. The HPLC method was validated according to the ICH guidelines. The limit of detection and lower limit of quantitation were 0.05 µg/ml and 0.1 µg/ml respectively. The recovery rate of DFMQ-19 from blood samples was >81% of the spiked amount. The RSD of the intra- and inter-day precisions was within 7.5%, and RE of accuracy was between -14.4% and 4.5%. This method was successfully applied to the pharmacokinetic study after administration of DFMQ-19. The pharmacokinetic parameters, such as half-life (t1/2 ), mean residence time (MRT), maximum concentration (Cmax ) were determined. Based on these pharmacokinetic parameters, the oral bioavailability of DFMQ-19 was calculated to be 13.42% in rat. This article is protected by copyright. All rights reserved. HIGHLIGHTS: HPLC method was validated to quantify DFMQ-19 in rat plasma I.S is one of the structural analogs of the analyte The HPLC method was validated according to the ICH guidelines The oral bioavailability of DFMQ-19 was 13.42% in rat.

Pharmacokinetic and Metabolic Characteristics of Herb-Derived Khellactone Derivatives, A Class of Anti-HIV and Anti-Hypertensive: A Review.

A vast number of structural modifications have been performed for khellactone derivatives (KDs) that have been widely concerned owing to their diverse biological properties, including anti-hypertension, anti-HIV, reversing P-glycoprotein (P-gp) mediated multidrug resistance, and anti-inflammation effects, to find the most active entity. However, extensive metabolism of KDs results in poor oral bioavailability, thus hindering the clinical trial performance of those components. The primary metabolic pathways have been revealed as hydrolysis, oxidation, acyl migration, and glucuronidation, while carboxylesterases and cytochrome P450 3A (CPY3A), as well as UDP-glucuronosyltransferases (UGTs) primarily mediate these metabolic pathways. Attention was mainly paid to the pharmacological features, therapeutic mechanisms and structure-activity relationships of KDs in previous reviews, whereas their pharmacokinetic and metabolic characteristics have seldom been discussed. In the present review, KDs' metabolism and their pharmacokinetic properties are summarized. In addition, the structure-metabolism relationships of KDs and the potential drug-drug interactions (DDIs) induced by KDs were also extensively discussed. The polarity, the acyl groups substituted at C-3' and C-4' positions, the configuration of C-3' and C-4', and the moieties substituted at C-3 and C-4 positions play the determinant roles for the metabolic profiles of KDs. Contributions from CYP3A4, UGT1A1, P-gp, and multidrug resistance-associated protein 2 have been disclosed to be primary for the potential DDIs. The review is expected to provide meaningful information and helpful guidelines for the further development of KDs.

DNA-functionalized MOF fluorescent probes for the enzyme-free and pretreatment-free detection of MicroRNA in serum.

MicroRNA (miRNA) is a promising biomarker that plays an important role in various biomedical applications, especially in cancer diagnosis. However, the current miRNA detection technology has inherent limitations such as complex operation, expensive testing cost and excessive detection time. In this study, a dual signal amplification biosensor based on DNA-functionalized metal-organic frameworks (MOFs) fluorescent probes, MFPBiosensor, was established for the enzyme-free and pretreatment-free detection of the colon cancer (CC) marker miR-23a. DNA-functionalized MOFs NH2-MIL-53(Al) (DNA@MOFs) were synthesized as fluorescent probes with specific recognition functions. A single DNA@MOF carries a large number of fluorescent ligands 2-aminoterephthalic acid (NH2-H2BDC), which can generate strong fluorescence signals after alkaline hydrolysis. Combined with catalyzed hairpin assembly (CHA), an efficient isothermal amplification technique, the dual signal enhancement strategy reduced matrix interference and sensitized the signal response. The established MFPBiosensor successfully detected extremely low levels of miRNA in complex biological samples with acceptable sensitivity and specificity. With a single detection cost of $0.583 and a test time of 50 min, the excellent inexpensive and rapid advantage of the MFPBiosensor is highlighted. More importantly, the subtle design enables the MFPBiosensor to achieve convenient batch detection, where miRNA in serum can be directly detected without any pretreatment process or enzyme. In conclusion, MFPBiosensor is a promising biosensor with substantial potential for commercial miRNA detection and clinical diagnostic applications of CC.

Development of double-layer poly (amino acid) modified electrochemical sensor for sensitive and direct detection of betamethasone in cosmetics.

Screening for illegal use of glucocorticoids (GCs) in cosmetics by electrochemical methods is extremely challenging due to the poor electrochemical activity of GCs. In this study, poly-L-Serine/poly-Taurine modified electrode (P(Tau)/P(L-Ser)/GCE) was prepared for sensitive and direct determination of betamethasone in cosmetics by a simple two-step in situ electropolymerization reaction. The relevant parameters of preparation and electroanalytical conditions were respectively studied, including the concentration of polymerization solution, the number of scanning circles and the scanning rate. The SEM and EDS mapping demonstrated successful preparation of P(Tau)/P(L-Ser)/GCE. The electro-catalytic properties of the obtained electrodes were investigated using cyclic voltammetry and differential pulse voltammetry methods, showing a remarkable improvement of sensitivity for the detection of betamethasone due to the synergic effect of both P(L-Ser) and P(Tau). In addition, we investigated the electrochemical reduction of betamethasone on the surface of modified electrode. It was found that the process was controlled by diffusion effect and involved the transfer of two electrons and two protons. Then the electrochemical sensor method based on P(Tau)/P(L-Ser)/GCE was established and delivered a linear response to betamethasone concentration from 0.5 to 20 µg mL-1 with a limit of detection of 32.2 ng mL-1, with excellent recoveries (98.1%-106.8%) and relative standard deviations (＜4.8%). Furthermore, the established electrochemical sensor method was compared with conventional HPLC method. The results showed that both of them were comparable. Moreover, the established electrochemical sensor method was with the merits of short analysis time, environmentally friendly, low cost and easy to achieve in-site detection.

Synthesis and α-glucosidase inhibitory activity evaluation of N-substituted aminomethyl-ß-d-glucopyranosides.

A series of N-substituted 1-aminomethyl-ß-d-glucopyranoside derivatives was prepared. These novel synthetic compounds were assessed in vitro for inhibitory activity against yeast α-glucosidase and both rat intestinal α-glucosidases maltase and sucrase. Most of the compounds displayed α-glucosidase inhibitory activity, with IC50 values covering the wide range from 2.3µM to 2.0mM. Compounds 19a (IC50=2.3µM) and 19b (IC50=5.6µM) were identified as the most potent inhibitors for yeast α-glucosidase, while compounds 16 (IC50=7.7 and 15.6µM) and 19e (IC50=5.1 and 10.4µM) were the strongest inhibitors of rat intestinal maltase and sucrase. Analysis of the kinetics of enzyme inhibition indicated that 19e inhibited maltase and sucrase in a competitive manner. The results suggest that the aminomethyl-ß-d-glucopyranoside moiety can mimic the substrates of α-glucosidase in the enzyme catalytic site, leading to competitive enzyme inhibition. Moreover, the nature of the N-substituent has considerable influence on inhibitory potency.

SIRT1 regulates CD40 expression induced by TNF-α via NF-ĸB pathway in endothelial cells.

BACKGROUND: Compelling evidence suggests that SIRT1, NAD(+)-dependent class III protein deacetylase, plays an important role in the prevention and treatment of atherosclerosis by counteracting inflammation. Cluster of differentiation 40 (CD40), as a pro-inflammatory cytokine, has been shown to participate in the pathophysiology of atherosclerosis. The relationship between SIRT1 and CD40, however, remained elusive. The present study was thus designed to explore the potential effect of SIRT1 on CD40 expression induced by tumor necrosis factor-α (TNF-α) and to disclose the underlying mechanism in CRL-1730 endothelial cells. METHODS: mRNA and protein expressions were identified by quantitative real-time PCR and Western blot respectively. Subcellular localization of SIRT1 was detected by immunofluorescence analysis. SIRT1 small-interfering RNA (siRNA) was carried out for mechanism study. RESULTS: TNF-α reduced SIRT1 expression and induced CD40 expression in CRL-1730 endothelial cells in a time- and concentration- dependent manner. Pretreatment with resveratrol (a potent SIRT1 activator) inhibited TNF-α-induced CD40 expression, while pretreatment with nicotinamide (class b HDACs inhibitor nicotinamide) or sirtinol (a known SIRT1 inhibitor), especially SIRT1 siRNA significantly augmented TNF-α-induced CD40 expression. The frther sudy idicated that PDTC (NF-ĸB inhibitor) pretreatment attenuated TNF-α-induced CD40 expression, and SIRT1 siRNA significantly augmented TNF-α-induced acetylated-NF-ĸB p65 (Lys310) expression. CONCLUSION: The present study provides the direct evidence that SIRT1 can inhibit TNF-α- induced CD40 expression in CRL-1730 endothelial cells by deacetylating the RelA/p65 subunit of NF-ĸB at lysine 310, which provides new insights into understanding of the anti-inflammatory and anti-athroscerotic actions of SIRT1.

Analysis and retention behavior of isoflavone glycosides and aglycones in Radix Astragali by HPLC with hydroxypropyl-ß-cyclodextrin as a mobile phase additive.

In order to determine isoflavone glycosides (calycosin-7-O-ß-D-glucoside and formononetin-7-O-ß-D-glucoside) and aglycones (calycosin and formononetin), a simple HPLC method with isocratic elution employing hydroxypropyl-ß-cyclodextrin (HP-ß-CD) as a mobile phase additive was developed. Various factors affecting the retention of isoflavone glycosides and aglycones in the C(18) reversed-phase column, such as the nature of cyclodextrins, HP-ß-CD concentration, and methanol concentration, were systematically studied. The results show that HP-ß-CD, as a very effective mobile phase additive, can markedly reduce the retention of isoflavone glycosides and aglycones, and the decrease magnitudes of isoflavone aglycones are more than those of their glycosides. The role of HP-ß-CD in the developed HPLC method is attributed to the formation of the inclusion complexes between isoflavone glycosides (or aglycones) and HP-ß-CD. So, the apparent formation constants of the isoflavone glycosides (or aglycones)/HP-ß-CD inclusion complexes also were investigated. Isoflavone glycosides (and aglycones) form the 1:1 inclusion complexes with HP-ß-CD, and the isoflavone aglycones/HP-ß-CD complexes are more stable than the isoflavone glycosides/HP-ß-CD complexes. Finally, the optimized method was successfully applied for the determination of isoflavone glycosides and aglycones in Radix Astragali samples.

Separation and determination of resibufogenin and cinobufagin in Chansu using reversed-phase liquid chromatography with γ-cyclodextrin as mobile-phase modifier.

A simple, accurate, sensitive, and robust reversed-phase high-performance liquid chromatography (HPLC) method employing cyclodextrins as mobile phase additives has been developed in order to separate and determine resibufogenin and cinobufagin. Various factors affecting the separation for them, such as the nature of cyclodextrins, organic solvent, the concentration of γ-cyclodextrin, and temperature, were systematically studied. γ-cyclodextrin, as an effective mobile phase additive, can markedly improve the separation for resibufogenin and cinobufagin. The role of γ-cyclodextrin in the developed HPLC method is attributed to the formation of the inclusion complex between resibufogenin (or cinobufagin) and γ-cyclodextrin. So, the apparent formation constant (K(f) ) of the resibufogenin (or cinobufagin)/γ-cyclodextrin inclusion complex and the thermodynamic parameters of the inclusion process also were investigated. Resibufogenin (or cinobufagin) forms the 1:1 inclusion complexes with γ-cyclodextrin, and the resibufogenin/γ-cyclodextrin complex is more stable than the cinobufagin/γ-cyclodextrin complex. The K(f) values of resibufogenin and cinobufagin decrease with the increase of the temperature. The thermodynamic parameters of the inclusion reveal that the inclusion process between resibufogenin (or cinobufagin) and γ-cyclodextrin is spontaneous, exothermic, and enthalpically driven. Finally, the optimized method was successfully applied to separate and determine of resibufogenin and cinobufagin in the different Chansu (Bufonis venenum) samples.

Multi-template imprinted solid-phase microextraction coupled with UPLC-Q-TOF-MS for simultaneous monitoring of ten hepatotoxic pyrrolizidine alkaloids in scented tea.

Pyrrolizidine alkaloids (PAs) are a series of ubiquitous natural toxins in flowering plants, which are associated with serious hepatic disease in humans. However, the simultaneously fast and sensitive monitoring of different PAs are still challenge because of the diversity of PAs and huge amount of interference in complex samples, such as scented tea samples. In this study, molecularly imprinted solid phase microextraction (MIP-SPME) fibers were fabricated by using multi-template imprinting technique for selective recognition and efficient enrichment of different PAs from scented teas. MIP-SPME could be used for selective adsorption of ten types of PAs through specific recognition cavity and strong ionic interaction, including senecionine, lycopsamine, retrorsine, heliotrine, lasiocarpine, monocrotaline, echimidine, erucifoline, europine and seneciphylline. The extraction parameters were also optimized including extraction time, elution solvent and elution time. Then, ultra performance liquid chromatography- quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS) coupled with MIP-SPME method was developed for fast, simple, sensitive and accurate determination of ten PAs in scented teas. The established method was validated and presented satisfactory accuracy and high precision. It was also successfully applied for simultaneous determination of ten PAs in different scented tea samples. PAs were found in most of these scented tea samples, which suggest the cautious use of scented tea for consumers.

Highly efficient amino-functionalized aluminum-based metal organic frameworks mesoporous nanorods for selective extraction of hydrocortisone in pharmaceutical wastewater.

Hydrocortisone (HC), as a common steroid hormone drug, is also one of the key intermediates involved in the synthesis of multiple steroid hormone drugs. Residual HC in pharmaceutical wastewater frequently pollutes environmental water as steroid hormone contaminant and possesses great threat to human health as well as sustainable development of the ecosystem. Herein, in order to develop a highly efficient adsorbent system for selective enrichment and detection of HC in pharmaceutical wastewater, a novel amino-functionalized aluminum-based metal organic frameworks (Al-MOFs@NH2) mesoporous nanorod is fabricated, in which 2-aminoterephthalic acid plays a dual role as organic linker and functional modification unit. The resultant Al-MOFs@NH2 not only exhibits stable mesoporous structure but also has large specific surface area (849.76 m2 g-1) and plentiful binding sites, which significantly increases the adsorption capacity for HC. Under the promotion of hydrogen bonding and hydrophobic interaction together, Al-MOFs@NH2 possesses high adsorption capacity (218.53 mg g-1) for HC, as well as shows satisfactory selectivity for HC and other steroid hormones. Moreover, a method using Al-MOFs@NH2 as solid phase extraction adsorbents combined with high performance liquid chromatography (HPLC) has been developed to specifically enrich and detect trace amount of HC in pharmaceutical wastewater. The developed method has a low limit of detection (LOD) (0.5×10-3 µg mL-1) and shows satisfactory recoveries for HC (75.9%-102.5%) with an acceptable relative standard deviation (RSD). These results demonstrate that the facile one-step preparation and excellent adsorption capacity makes Al-MOFs@NH2 attractive to capture and remove environmental steroid hormone pollutants. More importantly, the method proposed in this work is expected to provide a prospective solution for analysis of strong bioactive contaminants in pharmaceutical wastewater.

[Determination of supermolecular inclusion constants of hydroxylpropyl-beta-cylcodextrin with imperatorin and isoimperatorin by phase solubility method].

OBJECTIVE: To study the supermolecular interaction between different concentrations of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and imperatorin (IM) and isoimperatorin (ISO) using phase solubility analysis. METHODS: Different concentrations of hydroxypropyl-beta-cyclodextrin were prepared, added overdose of imperatorin or isoimperatorin, made a phase solubility diagram. RESULTS: The relationship of phase solubility was approximatively linear and the model of inclusion compound was AL and the inclusion ratio of IM, ISO versus HP-beta-CD was 1: 1. The inclusion constants were 214.4, 587.2 L/mol respectively. CONCLUSIONS: Supermolecular inclusion of HP-beta-CD of imperatorin/isoimperatorin could evidently increase the solubility of imperatorin and isoimperatorin, the enhancing effect of isoimperatorin solubility is better than that of imperatorin.

Metal-organic framework grafted with melamine for the selective recognition and miniaturized solid phase extraction of aristolochic acid â from traditional Chinese medicine.

Aristolochic acid Ⅰ is a nephrotoxic compound and exist in some traditional Chinese medicines at trace level. Up to now, specific enrichment of aristolochic acid Ⅰ remains important procedure and key problem in its analysis. In this study, melamine was proposed as the recognition unit and grafted on the surface of metal-organic framework to fabricate a specific material for aristolochic acid Ⅰ. This material was prepared by using a two-step strategy and the preparation process was optimized. The physical and chemical properties were investigated using scanning electron microscopy, Fourier-transfer infrared spectroscopy, X-ray diffraction and nitrogen adsorption-desorption techniques. Adsorption properties were evaluated by binding experiments. The melamine modified material exhibited a uniform morphology, high specific surface area (460.20 m2 g-1), high adsorption capacity (25.57 mg g-1), fast mass transfer rate and excellent selectivity. Further, a specific and sensitive method was established by using this material as adsorbent of mini-solid phase extraction. The limit of detection was as low as 0.02 µg mL-1. Therefore, melamine modified metal-organic framework is an ideal adsorbent for the recognition and enrichment of aristolochic acid Ⅰ.

Facile covalent preparation of carbon nanotubes / amine-functionalized Fe3O4 nanocomposites for selective extraction of estradiol in pharmaceutical industry wastewater.

As a typical steroid hormone drug, estradiol (E2) is also one of the most frequently detected endocrine disrupting chemicals (EDCs) in the aquatic environment. Herein, in response to the potential risk of E2 in steroid hormone pharmaceutical industry wastewater to human and wildlife, a novel carbon nanotubes / amine-functionalized Fe3O4 (CNTs/MNPs@NH2) nanocomposites with magnetic responsive have been developed for the enrichment and extraction of E2 in pharmaceutical industry wastewater, where amino-functionalized Fe3O4 magnetic nanoparticles (MNPs@NH2) were used as a magnetic source. The resultant CNTs/MNPs@NH2 possessed both the features of CNTs and desired magnetic property, enabling to rapidly recognize and separate E2 from pharmaceutical industry wastewater. Meanwhile, the CNTs/MNPs@NH2 had good binding behavior toward E2 with fast binding kinetics and high adsorption capacity, as well as exhibited satisfactory selectivity to steroidal estrogen compounds. Furthermore, the change of pH value of aqueous phase in adsorption solvent hardly affected the adsorption of E2 by CNTs/MNPs@NH2, and the adsorption capacity of E2 ranged from 19.9 to 17.2 mg g-1 in the pH range of 3.0 to 11.0, which is a latent advantage of the follow-up development method to detect E2 in pharmaceutical industry wastewater. As a result, the CNTs/MNPs@NH2 serving as a solid phase extraction medium were successfully applied to efficiently extract E2 from pharmaceutical industry wastewater. Therefore, the CNTs/MNPs@NH2 nanocomposites could be used as a potential adsorbent for removing steroidal estrogens from water. More importantly, the developed method would provide a promising solution for the monitoring and analysis of EDCs in pharmaceutical industry wastewater.

Different pharmacological properties of the optical isomers of MN9202, a novel 1,4-dihydropyridine Ca+ channel modulator, in rat ventricular myocytes.

1. We have shown previously that 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid pentyl methyl ester (MN9202), a new 1,4-dihydropyridine Ca(2+) channel modulator, has significant hypotensive effects and favourable pharmacokinetic characteristics. As a chiral molecule, MN9202 has two optical isomers. The aim of the present study was to evaluate the pharmacological properties of the two enantiomers. 2. The two enantiomers, S-(-)- and R-(+)-MN9202, were obtained by HPLC. At 1 micromol/L, both racemic MN9202 and S-(-)-MN9202 decreased the contractility of rat ventricular myocytes by 54.0 and 64.4%, respectively, compared with control, whereas R-(+)-MN9202 enhanced cell shortening by 10.1%. At 1 micromol/L, racemic MN9202 markedly reduced calcium transient (CaT) and L-type Ca(2+) channel current (I(Ca,L)) by 60.0 and 50.7%, respectively, whereas the reductions in CaT and I(Ca,L) produced by 1 micromol/L S-(-)-MN9202 were greater still (62.2 and 65.7%, respectively). In contrast, 1 micromol/L R-(+)-MN9202 increased CaT and I(Ca,L) by 11.4 and 10.6%, respectively. Furthermore, findings from kinetics studies of I(Ca,L) revealed that the steady state inactivation curve of I(Ca,L) was shifted towards a hyperpolarizing potential by S-(-)-MN9202, but towards a depolarizing potential by R-(+)-MN9202. These results demonstrate different effects of R-(+)-MN9202 and S-(-)-MN9202. 3. In conclusion, the findings of the present study suggest that the chirality of MN9202 results in opposing pharmacological properties of its two enantiomers: S-(-)-MN9202 may be responsible for the therapeutic effects of racemic MN9202, whereas R-(+)-MN9202 contributes to it unwanted effects. The findings of the present study also indicate that MN9202 may be used as a new probe with which to investigate the structure-function relationships of Ca(2+) channels.

The influence of chirality, physicochemical properties, and permeation enhancers on the transdermal permeation of amlodipine across rat skin.

PURPOSE: This study was aimed at investigating the possible relationship between the physical properties and the permeation of S-amlodipine and RS-amlodipine and studying the possible enantioselectivity of permeation of amlodipine in the presence and absence of enhancers, such as terpene enhancers and ethanol. METHOD: The solubility of S-amlodipine and RS-amlodipine was measured using the shake-flask method. The thermodynamic properties were investigated by differential scanning calorimetry (DSC). The type of racemate amlodipine was investigated by DSC and Fourier transform infrared spectroscopy (FTIR). The permeability of racemate and enantiomers of amlodipine through rat epidermis in vitro was investigated using the modified Franz diffusion cell. RESULTS: The aqueous solubility of S-amlodipine was higher than that of RS-amlodipine. The melting temperature and enthalpy of fusion of S-amlodipine were lower than those of RS-amlodipine. RS-amlodipine was a racemic compound. The permeation of the enantiomers of amlodipine from RS-amlodipine reservoir showed no significant differences in the presence and absence of enhancers, but the permeation of S-amlodipine from S-amlodipine reservoir was significantly higher than that of RS-amlodipine from RS-amlodipine reservoir 30% ethanol, 50% ethanol, and terpene enhancers could not influence the difference in permeation between S-amlodipine and RS-amlodipine, but 75% ethanol could reduce the difference. CONCLUSION: These results suggested that there was no enantioselectivity of the enantiomers of amlodipine from RS-amlodipine reservoir in the presence and absence of enhancers, but the differences in physical properties between S-amlodipine and RS-amlodipine led to the difference in permeation across rat skins.