A simple and sensitive HPLC-MS/MS assay for the quantitation of montelukast in cell-based systems in vitro pulmonary drug permeability study.

Montelukast is a potent and selective antagonist of the cysteinyl leukotriene receptor 1 subtype (CysLT1) and widely used in the form of oral tablets and granules for asthma prophylaxis and treatment. Recently, due to the pulmonary inhaled administration can limit montelukast distribution in the systemic circulation, avoid the first-pass metabolism and have better therapeutic effects in respiratory disease treatment, explore alternative routes of administration, like delivery of montelukast via an inhaled, is a new research trend for montelukast. The aim of the current study was to develop and validate a simple, accurate, highly sensitive and selective liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for determination of montelukast in an in vitro cell-based pulmonary pharmacokinetics system model, which can be used to be a better understanding the fate of inhaled montelukast in the lungs. In this study, montelukast was extracted by protein precipitation with acetonitrile containing labeled montelukast. The chromatography was performed on an Agilent Eclipse plus C8 column (4.6 mm × 100 mm, 3.5 µm, Darmstadt, Germany) operating at 35 ◦C. The mobile phase consisted of acetonitrile: 20 mM ammonium formate buffer (80: 20, v/v), was delivered at a flow rate of 0.5 mL/min. montelukast and the internal standard were both eluted at 4.2 min. A linear (1/x2) relationship was used to perform the calibration over an analytical range from 0.5 to 600 ng/mL. The intra- and inter-batch precision expressed as CV for four QC samples including LLOQ range from 1.14 % to 6.25 %. The intra- and inter-batch accuracy for four concentrations of montelukast were in the range of 95.19%-104.1%. All the values for accuracy and precision were within the acceptance range. The method met all the bioanalytical method validation requirements by ICH and was suitable for the assay of montelukast which in the in vitro cell-based pulmonary pharmacokinetics system model.

Pharmacodynamic effects of Dan-hong injection in rats with blood stasis syndrome.

Dan-hong injection (DHI) is extracted from Salvia miltiorrhiza (SM) and Carthamus tinctorius (CT) and is widely used for the treatment of cardiovascular diseases. Our previous results showed DHI could improve hemorheology in rats. Since complex cellular interactions such as inflammation and oxidative stress are believed to be implicated in the pathogenesis of cardiovascular events, investigation of such pathological factors will contribute substantially to the understanding of the features and mechanisms of DHI. Therefore, in this study we used a rat model of blood stasis to explore the overall effects of DHI by detecting twenty three indexes, which were related to inflammation, immune response, vascular endothelial function, myocardial energy metabolism, oxidative stress, platelet aggregation, liver and renal function. Meanwhile, the interaction between SM and CT was discussed by comparing the effects of each single herb. DHI could significantly decrease the serum contents of IL-1ß, TNF-α, IL-6, IL-8, IgM, IgG, IgA, MPO, hs-CRP, MDA, LDH, CK-MB, PAF, ALP and Cr, while elevate NO, SOD, TP and UA levels, indicating that DHI could inhibit inflammation and platelet aggregation, thereby relieving immune response and peroxidation, protecting vascular endothelial and organ function, and then prevent and treat cardiovascular diseases. In terms of compatibility, SM and CT showed complementary effects on markers of inflammatory and oxidative status, vascular endothelial damage and myocardial energy metabolism. On the other hand, they counteracted each other and SM reduced the side effects of creatinine caused by CT. This study contributes to comprehensively understand the pharmacodynamics effects and mechanism of DHI.

[Effects of ozone stress on photosynthesis and dry matter production of rice II -you 084 under different Planting densities].

In order to investigate the effects of ozone stress on photosynthesis, dry matter production, non-structural carbohydrate and yield formation of rice, a free air ozone concentration enrichment (FACE) experiment was conducted. A super hybrid rice cultivar II-you 084 with 3 spacing levels, low plant density (LD, 16 hills per m2), medium (MD, 24 hills per m2) and high plant density (HD, 32 hills per m2), was grown in the field at current and elevated ozone concentrations (current × 1.5). The results were as follows: Elevated ozone significantly reduced leaf SPAD value of UI-you 084 by 6%, 11% and 13%, at 63, 77, and 86 days after transplanting, respectively. The declines in leaf net photosynthetic rate, stomatal conductance and transpiration rate at filling stage increased significantly on ozone stress over time. Ozone stress decreased dry matter production of rice by 46% from heading stage to plant maturity, thus reduced biomass yield by 25%. Elevated ozone decreased the concentration and accumulation of soluble carbohydrate and starch in stem of II-you 084 at jointing, heading and plant maturity, but significantly increased the dry matter transportation rate. No significant interaction was observed between ozone and planting density for photosynthesis, dry matter production and non-structural carbohydrate of rice. The above results indicated that elevated ozone reduced photosynthesis and growth of rice II-you 084 at late growth stage, which had no relationship with planting density.

Systematic chemical profiling of Citrus grandis 'Tomentosa' by ultra-fast liquid chromatography/diode-array detector/quadrupole time-of-flight tandem mass spectrometry.

Citrus grandis 'Tomentosa', as the original plant of the traditional Chinese medicine "Huajuhong", has been used as antitussive and expectorant in clinic for thousands of years. The fruit epicarp and whole fruit of this plant were both literarily recorded and commonly used. In the present study, an ultra-fast liquid chromatography coupled with diode-array detection and quadrupole/time-of-flight mass spectrometry (UFLC-DAD-Q-TOF-MS/MS) based chemical profiling method was developed for rapid holistic quality evaluation of C. grandis 'Tomentosa', which laid basis for chemical comparison of two medicinal parts. As a result, forty-eight constituents, mainly belonging to flavonoids and coumarins, were unambiguously identified by comparison with reference standards and/or tentatively characterized by elucidating UV spectra, quasi-molecular ions and fragment ions referring to information available in literature. Both of the epicarp and whole fruit samples were rich in flavonoids and coumarins, but major flavonoids contents in whole fruit were significantly higher than in epicarp (P<0.5). The proposed method could be useful in quality control and standardization of C. grandis 'Tomentosa' raw materials and its products. Results obtained in this study will provide a basis for quality assessment and further study in vivo.