Development of a method for determination of osmotic pump controlled-release tablets of lorcaserin hydrochloride in beagle dog plasma and its application to pharmacokinetic study / 中国药理学通报

Aim To develop an UPLC-MS/MS method to determine the concentration of lorcaserin hydrochloride in beagle plasma, and study the pharmacokinetics of osmotic pump controlled-release tablets of lorcaserin hydrochloride. Methods A randomized crossover design was used, carbamazepine as the internal standard(IS), and plasma protein precipitation with acetonitrile. The chromatographic was Phenomenex Polar C18 column(100 mm×2. 1 mm, 3 μm), and acetonitrile - water(containing 10 mmol·L-1 ammonium acetate and 0.1% formic acid)(40:60, V/V)was mobile phase. Multiple reaction monitoring mode and electrospray positive ionization were used to detect lorcaserin hydrochloride. The MS/MS ion transitions were monitored at m/z 196.2→129.2 for lorcaserin hydrochloride and m/z 237→194.1 for carbamazepine, respectively. Results The linear range was 1 to 500 μg·L-1(r=0.999 2), the extraction recovery rate ranged from 87.70% to 89.70%, the precision RSD was 9.7%. The accuracy and matrix effect met the requirements, and the stability of lorcaserin hydrochloride was good in -20 ℃ refrigerator for 45 d, repeated freezing and thawing for three times, placed at room temperature for 24 h, and the disposed samples placed in automatsampler for 6 h were stable. The main pharmacokinetic parameters of the controlled-release tablet and immediate-release tablet were as follows:Tmax was(8.00±1.27)h and(1.00±0.13)h, Cmax was(70.56±3.73)μg·L-1 and(176.33±16.73)μg·L-1, and AUC0-t was(966.33±7.56)μg·h·L-1 and(973.05±69.09)μg·h·L-1, respectively. Conclusions The established UPLC-MS/MS method can be used to study the pharmacokinetics of lorcaserin hydrochloride in the plasma of beagle dogs, and osmotic pump controlled-release tablets has sustained release effect.

Analysis of Effect of Realgar with Different Compatibility Proportions on Transitional Constituents of Indigo Naturalis in Rat Serum Based on UPLC-Q-TOF-MS/MS / 中国实验方剂学杂志

Objective:To investigate the effect of different dose of Realgar compatible with Indigo Naturalis on the transitional constituents of Indigo Naturalis in rat serum based on the compatibility of Qinghuangsan.Method:Indigo Naturalis test solution, the drug-containing serum of three different proportions of Qinghuangsan (10 g of Indigo Naturalis compatible with 52.5, 105, 210 mg of Realgar for group A, B and C, respectively) and blank serum were detected by UPLC-Q-TOF-MS/MS, in combination with the chemical components identified in Indigo Naturalis test solution, the differences of transitional constituents of Indigo Naturalis in rat serum from the group A, B and C were analyzed. HL-60 cells (human leukemia cells) were treated with the three groups of Qinghuangsan drug-containing serum and the effect of drug-containing serum on the activity of HL-60 cells was detected by cell counting kit-8 (CCK-8) assay.Result:A total of 19, 22, 25 of transitional constituents were detected in Qinghuangsan drug-containing serum from group A, B and C, respectively. The three groups of drug-containing serum all contained 5 prototype components from Indigo Naturalis test solution, including tryptanthrin, indigo, indirubin, 2-aminobenzoic acid and N-phenyl-2-naphthylamine, respectively. The results of CCK-8 assay showed that Qinghuangsan drug-containing serum of group C had the strongest inhibitory effect on HL-60 cells.Conclusion:After fixed Indigo Naturalis dose, with the increase of Realgar dose, the transitional constituents in rat serum increase and the inhibitory effect on HL-60 cells also gradually enhances, which indicates that Realgar may promote the absorption of active components in Indigo Naturali in vivo, thus enhance the efficacy, further explains the compatibility law and pharmacodynamic material basis of different proportions of Realgar and Indigo Naturalis.

Comparative study on serum transitional components of Huatan Jiangqi Capsules in rats under pathological and physiological status / 中国中药杂志

The differences of transitional components and metabolic processes of Huatan Jiangqi Capsules(HTJQ) in rats under normal physiological and pathological conditions of COPD were analyzed by UPLC-Q-TOF-MS. The rat COPD model was established by passive smoking and intratracheal instillation of lipopolysaccharide. After the normal and COPD model rats were douched with HTJQ, the blood was collected from hepatic portal vein and the drug-containing serum samples were prepared by methanol precipitation of protein. Then, 10 batches of drug-containing serum samples of HTJQ were prepared and analyzed by UPLC serum fingerprint to evaluate the quality and stability of drug-containing serum samples. UPLC-Q-TOF-MS was used to collect the mass spectrometric information of the transitional components. Twenty-eight transitional components of HTJQ in normal rats and 25 transitional components of HTJQ in COPD model rats were identified by UPLC-Q-TOF-MS. Under pathological and physiological conditions, there were not only the same transitional components in rat serum, but also corresponding differences. Further studies showed that there were also differences in the metabolic process of transitional components between the two conditions. In normal rats, most of the metabolic types of transitional components were phase I reactions. In COPD model rats, phase Ⅰ reactions decreased and phase Ⅱ reactions increased correspondingly. With UPLC-Q-TOF-MS technology, the differences of transitional components and the metabolism process of HTJQ in rats under normal physiological and pathological conditions were analyzed. The results showed that types of transitional components and the activity of some metabolic enzymes would be changed in COPD pathological state, which would affect the metabolic process of bioactive components in vivo. It laid a foundation for further elucidating the metabolic process and pharmacodynamic substance basis of HTJQ.

Determination of hainanolidol and its pharmacokinetics in rat plasma by UPLC / 中国药理学通报

Aim To establish a UPLC method for the determination of the concentration of hainanolidol in plasma of rats, and study the pharmacokinetics of hain-anolidol in rat plasma after single dose i. v. administra-tion of hainanolidol (1, 2, 4 mg·kg-1). Methods The UPLC method for the determination of hainanolidol in rat plasma was established using hainanolide as in-ternal standard. The mobile phase was methanol-water (47 ∶ 53), the flow rate was 0.17 mL·min-1, and the detection wavelength was UV 326 nm. The plasma concentration of hainanolidol in rats was determined by UPLC after single-dose intravenous injection in rats with 1, 2 and 4 mg·kg-1of hainanolidol, and the pharmacokinetic parameters were calculated by DAS2.1. Results The result of calibration curve was linear over the range of 0.05 ~10.00 mg·L-1( r = 0.999 6) . The lower limit of quantification was 0.05 mg·L-1. The intra-day and inter-day precision were both lower than 5% , and the extraction recoveries were higher than 85% , respectively. The validated method was successfully applied to the pharmacokinetic study after i. v administration of hainanolidol in rats with do-ses of 1, 2 and 4 mg·kg-1. The T1/2was (39.82 ± 0.92), (40.11 ± 0.79) and (41.61 ± 2.07) min, respectively. The AUC0-twas ( 65.77 ± 1.08 ) , (130.48 ± 1.26) and (268.75 ± 1.24) min·mg· L-1, respectively. Conclusion A simple and specific UPLC method for the analysis of hainanolidol is suc-cessfully developed, which could be applied to phar-macokinetic study in rat plasma.

Roles of the cross talk between MAP kinases and Keap1-Nrf2-ARE signaling pathways in chronic obstructive pulmonary disease / 药学学报

Chronic obstructive pulmonary disease (COPD), a common preventable and treatable disease, is characterized by airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways. Its main pathological manifestations include airway inflammation, mucus hypersecretion, oxidative stress and apoptotic epithelial cells. Recent research suggests that MAP kinases and Keap1-Nrf2-ARE signaling pathway are involved in the pathological process of inflammation and oxidative stress. This review explores the potential role of the cross talk of these signaling pathways in airway inflammation, mucus hypersecretion, oxidative stress and apoptotic epithelial cells. To clarify the roles of cross talk between MAP kinases and Keap1-Nrf2-ARE signaling pathway, we also focus on the drugs related to that in the treatment of COPD, and it provides ideas for more drug research in the treatment of COPD.

The application of biotechnology in medicinal plants breeding research in China / 中国结合医学杂志

Breeding is not only an important area of medicinal plants research but also the foundation for the superior varieties acquirement of medicinal plants. The rise of modern biotechnology provides good opportunities and new means for medicinal plants breeding research in China. Biotechnology shows its technical advantages and new development prospects in breeding of new medicinal plants varieties with high and stable yield, good quality, as well as stress-resistance. In this paper, we describe recent advances, problems, and development prospects about the application of modern biotechnology in medicinal plants breeding research in China.

Effects of huatan jiangqi capsule on the levels of multi-drug resistance-associated protein 1 in the bronchial epithelial cells of model rats with chronic obstructive pulmonary disease / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effects of huatan jiangqi capsule (HJC) on the expression levels and functions of multi-drug resistance-associated protein 1 (MRP1) in the bronchial epithelial cells of chronic obstructive pulmonary disease (COPD) model rats, and to explore the mechanism of HJC for treating COPD.</p><p><b>METHODS</b>Twenty-four male wistar rats were randomly divided into the normal control group, the model group, and HJC group. Except the normal control group, the COPD rat model was established in the rest groups using quantitative stimulation with tobacco, SO2, and caroid aerosol rebreathing method. The indices of the post-treatment lung functions, the cell counts of bronchoalveolar lavage fluid (BALF), the pathological features of the lung tissue were observed. The concentration of LTC, in lung tissues was also examined by ELISA. The expression of MRP1 of the pulmonary tracheal epithelium was detected using immunohistochemical assay.</p><p><b>RESULTS</b>(1) The pulmonary compliance, the forced expiratory volume at 0. 3 second (FEV 0.3%)/the forced vital capacity (FVC), the peak expiratory flow, the maximum mid expiratory flow decreased more significantly in the model group than in the normal control group (P < 0.05). The aforesaid pulmonary function indices obviously increased in the HJC group when compared with the model group (P < 0.05). (2) The air inflammation was aggravated with obvious emphysema in the model group. The inflammation and emphysema occurred in the HJC group in a milder degree. (3) Compared with the normal control group, the levels of LTC4 significantly increased in the lung tissue of the model group and HJC group (P < 0.01). Compared with the model group, the levels of LTC4 significantly decreased in the lung tissues of the HJC group (P < 0.05). (4) Compared with the normal control group, the protein expression of the bronchial epithelial MRP1 significantly decreased in the model group (P < 0.01). Compared with the model group, the protein expression of the bronchial epithelial MRP1 were significantly enhanced in the HJC group (P < 0.05).</p><p><b>CONCLUSION</b>HJC could effectively alleviate the lung inflammation, postpone the occurrence and development of COPD possibly through effecting the functions and expressions of MRP1 in COPD rats.</p>

Quality evaluation of prepared slices of Paeonia lactiflon--determination of paeoniflorin by HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>To establish the quality criteria of the prepared slices of Paeonia lactiflon.</p><p><b>METHOD</b>RP-HPLC was used for the determination of paeoniflorin in 10 lots of samples by ultrasound-assisted extraction.</p><p><b>RESULT</b>The samples were extracted with 50% methanol. Seperation of the solution was performed on an ODS column with a mobile phase of acetonitrile-water (18:82), detected at 230 nm.</p><p><b>CONCLUSION</b>The method is simple, repeatable, accurate and applicable.</p>