Neomangiferin, a natural C-glucosyl xanthone, has recently received a great deal of attention due to its multiple biological activities. In this study, a rapid and sensitive ultra-high performance liquid chroma-tography tandem mass spectrometry (UHPLC–MS/MS) method for the quantification of neomangiferin in rat plasma was developed. Using chloramphenicol as an internal standard (IS), plasma samples were subjected to a direct protein precipitation process using methanol (containing 0.05% formic acid). Quan-tification was performed by multiple reactions monitoring (MRM) method, with the transitions of the parent ions to the product ions of m/z 583.1-330.9 for NG and m/z 321.1-151.9 for IS. The assay was shown to be linear over the range of 0.2–400 ng/mL, with a lower limit of quantification of 0.2 ng/mL. Mean recovery of neomangiferin in plasma was in the range of 97.76%–101.94%. Relative standard deviations (RSDs) of intra-day and inter-day precision were both o 10%. The accuracy of the method ranged from 94.20%to 108.72%. This method was successfully applied to pharmacokinetic study of neomangiferin after intravenous (2 mg/kg) and intragastric (10 mg/kg) administration for the first time. The oral absolute bioavailability of neomangiferin was estimated to be 0.53%7 0.08%with an elimination half-life (t1/2) value of 2.74 7 0.92 h, indicating its poor absorption and/or strong metabolism in vivo.

The previous pharmacokinetic methods can be only limited to drug analysis in vitro, which provide less information on the distribution and metabolismof drugs, and limit the interpretation and assessment of pharmacokinetics, the determination of metabolic principles, and evaluation of treatment effect. The objective of the study was to investigate the pharmacokinetic characteristics of gene recombination angiogenesis inhibitor Kringle 5 in vivo. The SPECT/CT and specific 131I-Kringle 5 marked by Iodogen method were both applied to explore the pharmacokinetic characteristics of 131I-Kringle 5 in vivo, and to investigate the dynamic distributions of 131I-Kringle 5 in target organs. Labeling recombinant angio-genesis inhibitor Kringle 5 using 131I with longer half-life and imaging in vivo using SPECT instead of PET, could overcome the limitations of previous methods. When the doses of 131I-Kringle 5 were 10.0, 7.5 and 5.0 g/kg, respectively, the two-compartment open models can be determined within all the metabolic process in vivo. There were no significant differences in t1/2α, t1/2β, apparent volume of distribution and CL between those three levels. The ratio of AUC(0 ? 1) among three different groups of 10.0, 7.5 and 5.0 g/kg was 2.56:1.44:1.0, which was close to the ratio (2:1.5:1.0). It could be clear that in the range of 5.0–10.0 g/kg, Kringle 5 was characterized by the first-order pharmacokinetics. Approximately 30 min after 131I-Kringle 5 was injected, 131I-Kringle 5 could be observed to concentrate in the heart, kidneys, liver and other organs by means of planar imaging and tomography. After 1 h of being injected, more radionuclide retained in the bladder, but not in intestinal. It could be concluded that 131I-Kringle 5 is mainly excreted through the kidneys. About 2 h after the injection of 131I-Kringle 5, the radionuclide in the heart, kidneys, liver and other organs was gradually reduced, while more radionuclide was concentrated in the bladder. The radionuclide was completely metabolized within 24 h, and the distribution of radioactivity in rats was similar to normal levels. In our study, the specific marker 131I-Kringle 5 and SPECT/CT were suc-cessfully used to explore pharmacokinetic characteristics of Kringle 5 in rats. The study could provide a new evaluation platform of the specific, in vivo and real-time functional imaging and pharmacokinetics for the clinical application of 131I-Kringle 5.

The inclusion complexes of poorly water-soluble cephalosporin, cefuroxime axetil (CFA), were prepared withβ-cyclodextrin (βCD) with or without addition of L-arginine (ARG) to improve its physicochemical properties. We also investigated the effect of ARG on complexation efficiency (CE) ofβCD towards CFA in an aqueous medium through phase solubility behaviour according to Higuchi and Connors. Although phase solubility studies showed AL (linear) type of solubility curve in presence and absence of ARG, the CE and association constant (Ks) ofβCD towards CFA were significantly promoted in presence of ARG, justifying its use as a ternary component. The solid systems of CFA withβCD were obtained by spray drying technique with or without incorporation of ARG and characterized by differential scanning ca-lorimetry (DSC), X-ray powder diffractometry (XRPD), scanning electron microscopy (SEM), and sa-turation solubility and dissolution studies. The molecular modeling studies provided a better insight into geometry and inclusion mode of CFA insideβCD cavity. The solubility and dissolution rate of CFA were significantly improved upon complexation withβCD as compared to CFA alone. However, ternary system incorporated with ARG performed better than binary system in physicochemical evaluation. In conclu-sion, ARG could be exploited as a ternary component to improve the physicochemical properties of CFA viaβCD complexation.

Hexafluoroisopropanol (HFIP)-induced sodium dodecyl sulfate/dodecyltrimethylammonium bromide (SDS/DTAB) catanionic surfactant coacervate extraction method coupled with high performance liquid chromatography (HPLC) was used to detect the migration of phthalates from disposable tablewares to drinking water. The concentration factors are larger than 82 and extraction recoveries over 53%for water samples spiked with 100 or 200 ng/mL phthalates. Limit of detection is in the range of 1.0–2.6 ng/mL. Good linearity with correlation coefficients larger than 0.9985 is obtained in the concentration of 20–1500 or 40–3000 ng/mL. Relative recoveries are from 82.4%to 123.6%for water samples spiked with 30/60, 250/500, and 1500/3000 ng/mL phthalates, respectively. Relative standard deviations (RSDs) are 0.4%–7.4% for intraday precision (n ? 5) and 0.6%–7.8% for interday precision (n ? 3). Four of studied phthalates are found in the drinking water samples prepared from four kinds of tablewares.

Methylene blue (MB) is a hydrophobic drug molecule, having importance both as a staining reagent and pharmaceutical agent. MB is strongly fluorescent, with an emission peak at 686 nm (λex 665 nm). In the study, the possibility of MB as an extrinsic fluorophore to study the micellization behavior of bile salts (BSs) was carried out. Since BSs are drug delivery systems, the solubilization of hydrophobic MB drug molecule by BSs was achieved and the nature of association of MB with BS media, namely sodium cholate (NaC) and sodium deoxycholate (NaDC) was evaluated. Change in the photophysical properties of MB is monitored through fluorescence intensity and fluorescence anisotropy at emission peak, 686 nm of MB. Molecular mechanics calculations were carried out to evaluate the MB–BS association. The estimated heat of formation,ΔHf values are–625.19 kcal/mol for MB–NaC and–757.48 kcal/mol for MB–NaDC. The photophysical study also revealed that MB reports the step-wise aggregation pattern of BSs media, as an extrinsic fluorescence probe.

Achillea millefolium and Achillea ptarmica are both plants belonging to the Asteracea family and are traditionally used for their medicinal properties. It has already been shown that some N-alkylamides (NAAs) are responsible for these pharmacological actions. Therefore, in the present study, the NAA content of the two plants was analytically characterised. Different extracts were prepared from the roots, the leaves, the stems and the flowers. The structures of NAAs have been assigned in ethanolic extracts of Achillea millefolium and Achillea ptarmica using high performance liquid chromatography – electrospray ionisation – mass spectro-metry (HPLC–ESI–MS) and gas chromatography–electron impact–mass spectrometry (GC–EI–MS). Using both analytical techniques, the structures of 14 and 15 NAAs have been assigned in Achillea ptarmica and Achillea millefolium, respectively. Structures of two new NAAs, previously never observed in Achillea ptarmica, were assigned: deca-2E,6Z,8E-trienoic acid 2-methylbutylamide (homospilanthol) or a related isomeric compound and deca-2E,4E-dienoic acid N-methyl isobutylamide. The structure of homospilanthol or a related isomeric compound was also assigned in Achillea millefolium for the first time.

In this work, an electrochemical sensor was fabricated for determination of an anthracycline, doxorubicin (DOX) as a chemotherapy drug in plasma based on multi-walled carbon nanotubes modified platinum electrode (Pt/MWCNTs). DOX was effectively accumulated on the surface of modified electrode and generated a pair of redox peaks at around 0.522 and 0.647 V (vs. Ag/AgCl) in Britton Robinson (B-R) buffer (pH 4.0, 0.1 M). The electrochemical parameters including pH, type of buffer, accumulation time, amount of modifier and scan rate were optimized. Under the optimized conditions, there was a linear correlation between cathodic peak current and concentration of DOX in the range of 0.05–4.0 μg/mL with the detection limit of 0.002 μg/mL. The number of electron transfers (n) and electron transfer-coe?cient (α) were estimated as 2.0 and 0.25, respectively. The constructed sensor displayed excellent precision, sensitivity, repeatability and selectivity in the determination of DOX in plasma. Moreover, cyclic voltammetry studies of DOX in the presence of DNA showed an intercalation mechanism with binding constant (Kb) of 1.12×105 L/mol.

Interaction between bovine serum albumin (BSA) and phosphorus heterocycles (PHs) was studied using multi-spectroscopic techniques. The results indicated the high binding a?nity of PHs to BSA as it quenches the intrinsic fluorescence of BSA. The experimental data suggested the fluorescence quenching mechanism between PHs and BSA as a dynamic quenching. From the UV–vis studies, the apparent association constant (Kapp) was found to be 9.25×102, 1.27×104 and 9.01×102 L/mol for the interaction of BSA with PH-1, PH-2 and PH-3, respectively. According to the F?rster's non-radiation energy transfer (FRET) theory, the binding distances between BSA and PHs were calculated. The binding distances (r) of PH-1, PH-2 and PH-3 were found to be 2.86, 3.03, and 5.12 nm, respectively, indicating energy transfer occurs between BSA and PHs. The binding constants of the PHs obtained from the fluorescence quenching data were found to be decreased with increase of temperature. The negative values of the thermodynamic parametersΔH,ΔS andΔG at different temperatures revealed that the binding process is spontaneous;hydrogen bonds and van der Waals interaction were the main force to stabilize the complex. The microenvironment of the protein-binding site was studied by synchronous fluorescence and circular dichroism (CD) techniques and data indicated that the conformation of BSA changed in the presence of PHs. Finally, we studied the BSA-PHs docking using AutoDock and results suggest that PHs is located in the cleft between the domains of BSA.

A stability-indicating reverse phase–high performance liquid chromatography (RP–HPLC) method was developed and validated for the determination of atazanavir sulfate in tablet dosage forms using C18 column Phenomenix (250 mm×4.6 mm, 5μm) with a mobile phase consisting of 900 mL of HPLC grade methanol and 100 mL of water of HPLC grade. The pH was adjusted to 3.55 with acetic acid. The mobile phase was sonicated for 10 min and filtered through a 0.45μm membrane filter at a flow rate of 0.5 mL/min. The detection was carried out at 249 nm and retention time of atazanavir sulfate was found to be 8.323 min. Linearity was observed from 10 to 90μg/mL (coefficient of determination R2 was 0.999) with equation, y=23.427x+37.732. Atazanavir sulfate was subjected to stress conditions including acidic, alkaline, oxidation, photolysis and thermal degradation, and the results showed that it was more sensitive towards acidic degradation. The method was validated as per ICH guidelines.

In this study, we developed and validated a fast, specific, sensitive, precise and stability-indicating high performance liquid chromatography (HPLC) method to determine the drug apocynin in bovine serum albumin (BSA) nanoparticles. Chromatographic analyses were performed on an RP C18 column and using a photodiode array detector at a wavelength of 276 nm. Mobile phase consisted of a mixture of acetonitrile and 1%acetic acid (60:40, v/v), and it was eluted isocratically at a flow rate of 0.8 mL/min. The retention time of apocynin chromatographic peak was 1.65 min. The method was linear, precise, accurate and specific in the range of 5–100μg/mL. The intra-and inter-day precisions presented relative standard deviation (RSD) values lower than 2%. The method was robust regarding changes in mobile phase proportion, but not for flow rate. Limits of detection and quantitation were 78 ng/mL and 238 ng/mL, respectively. Apocynin was exposed to acid and alkali hydrolysis, oxidation and visible light. The drug suffered mild degradation under acid and oxidation conditions and great degradation under alkali conditions. Light exposure did not degrade the drug. The method was successfully applied to determine the encapsulation efficiency of apocynin in BSA nanoparticles.