Objective: To establish a rapid and accurate method for the determination of 15 chemical drugs which were illegally added into the slimming Chinese patent medicines (CPM) and health foods. Methods: The UPLC-MS/MS method was adopted. The samples were extracted with methanol by ultrasonic processing and separated on a Waters Acquity BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with 0.1% formic acid methanol (A) -0.1% formic acid water (B) as mobile phase by gradient elution (0-3 min, 33%-45% A; 3-5 min, 45%-55% A; 5-7 min, 55%-70% A; 7-9 min, 70%-80% A; 9-10 min, 80%-90% A; 10-11 min, 90%-33% A; 11-13 min, 33% A at a flow rate of 0.2 mL/min, and the column temperature was 40℃. A positive-ion (ESI+) source and an MRM mode were used to separate and quantitatively determine 15 chemical drugs. The obtained molecular ions, fragment ions, and retention time for MRM channels were used to identify the 15 kinds of drugs by comparison with those of reference substances. The obtained peak areas were used to determine the accurate contents of chemical drugs in CPM and the health foods. Results: A good resolution of 15 kinds of chemical drugs, including terbutaline hydrochloride, ephedrine hydrochloride, theophylline, caffeine, doxofylline, clenbuterol hydrochloride, tulobuterol hydrochloride, bambuterol hydrochloride, fenfluramine hydrochloride, furosemide, indapamide, phenolphthalein, sibutramine hydrochloride, N-demethylated sibutramine hydrochloride, and hydrochloric acid N,N-dinor sibutraminel, was obtained under this UPLC and MS/MS condition. The limits of qualitation and quantitation were in the range of 0.1-5.0 ng/g and 0.3-15.0 ng/g. The standard addition recoveries were in the range of 91.8%-110.8%. In the 86 batches of samples (including capsules, granules, and other different matrix types) were detected in the 74 batches of added chemicals, the positive rate was 86.0%. Sibutramine hydrochloride (39 batches), furosemide (20 batches), phenolphthalein (23 batches), theophylline (1 batch), and caffeine (15 batches) were checked out in the samples, 22 batches of which two kinds were checked out, one batch of which three kinds were checked out. By contrast, the products which were not clearly marked manufacturer illegally added more seriously. Conclusion: The method is simple, accurate, and highly sensitive, which can be used for the determination of illegally added chemical drugs in slimming CPM and health foods.

It is the objective of this paper to study pharmacokinetics-pharmacodynamics (PK-PD) characteristics of ginsenoside Rg1 and Rb1 on the effect of inducing nitric oxide (NO) release after intravenous administration of Shengmai injection to rats with myocardial ischemia. The model of myocardial ischemia rats was produced by subcutaneous injection of isoproterenol. The serum samples were collected at different time points after intravenous administration of Shengmai injection to rats with the dose of 10.8 mL x kg(-1). The concentrations of ginsenoside Rg1 and Rb1 in serum were determined, and then the concentration-time curves were drawn. Pharmacokinetic parameters of ginsenoside Rg1 and Rb1 were calculated after the construction of pharmacokinetic models. Meanwhile, NO2- and NO3-, the metabolites of NO, in serum were determined, and then the effect-time curve was drawn. The combined PK-PD model was established based on the theory of effect compartment by Sheiner et al. Then pharmacodynamic parameters were calculated. The results indicated that the pharmacokinetics of ginsenoside Rg1 and Rb1 conformed to a two-compartment model. Ginsenoside Rg1 and Rb1 exhibited quick and slow elimination in rats respectively. The effect of Shengmai injection on inducing NO release did not relate directly with and lagged behind the concentrations of ginsenoside Rg1 and Rb1 in serum. The effect exhibited good correlation with ginsenoside Rg1 and Rb1 levels in effect compartment. The relationship between effect and serum concentration fits Sigmoid-E(max) model. This study successfully established the combined PK-PD model of ginsenoside Rg1 and Rb1 after intravenous administration of Shengmai injection to rats. The model can efficiently predict the concentration and effect of Shengmai injection in vivo.
Administration, Intravenous ; Animals ; Ginsenosides ; administration & dosage ; pharmacokinetics ; Humans ; Male ; Myocardial Ischemia ; drug therapy ; metabolism ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley

The disease incidence of aortic dissecting aneurysm showed an increasing tendency.Recently,the clinical application of endovascular stent-graft implantation received good results in treating aortic dissecting aneurysm,which is characterized by minimally invasive,safe,with high success rates.However,the chosen of anesthesia is still in dispute.Local anesthesia,intraspinal anesthesia and general anesthesia can be used in this operation.The investigation demonstrated that intubation general anesthesia is more security in this operation with less complication,which is conductive to controlling blood pressure and braking conditions.

OBJECTIVETo predict human intestinal absorption and permeability coefficients in Caco-2 cell monolayers from net polar atomic charges of drug molecules.

METHODSThe net atomic charges and the volumes of drug molecules were obtained with the semiempirical self-consistent field molecular orbital calculation CNDO/2 method and Mont Carlo method respectively, using the minimum energy conformation obtained from the optimization of the standard molecular geometry with the molecular mechanics MM+ method. The stepwise multiple regression analysis was used to obtain the correlation equations.

RESULTBoth percent of human intestinal absorption and permeability coefficients in Caco-2 cell monolayers of drug molecules were well correlated with the sum of the net atomic charges of all hydrogen-bonding donors (sigmaQH) and the sum of the net atomic charges of all hydrogen-bonding acceptors (sigmaQN, 0). The more the net positive atomic charges of hydrogen-bonding donors and the net negative atomic charges of hydrogen-bonding acceptors, the less were the percent human intestinal absorption and permeability coefficients in Caco-2 cell monolayers of drug molecules.

CONCLUSIONDrug absorption in human intestines is closely related with its hydrogen-bonding potential. The drug molecules with weaker hydrogen-bonding potential have greater percent human intestinal absorption. The net polar atomic charges can be computed simply, so they can be used in high throughput screening of oral drugs.

Adrenergic beta-Antagonists ; pharmacokinetics ; Biological Transport ; physiology ; Caco-2 Cells ; Cell Membrane Permeability ; physiology ; Humans ; Hydrogen Bonding ; Intestinal Absorption ; Models, Chemical ; Molecular Structure ; Pharmaceutical Preparations ; metabolism ; Regression Analysis

OBJECTIVETo predict the plasma protein binding rate of cephalosporins from their molecular structural parameters.

METHODSThe minimum energy conformations of cephalosporins were obtained from the optimization of the standard molecular geometry with the semiempirical self-consistent field molecular orbital calculation AM1 method; Mont Carlo method was used to calculate the polar molecular surface areas; the stepwise multiple regression analysis was used to obtain the correlation equations.

RESULTSThe plasma protein binding rate of cephalosporins (fb) was well correlated with their molecular weights (MW) and surface areas of hydrogen-bonding donors (SH). The regression equation was: fb=0.5057+2.861x10(-3) MW-0.1572SH+4.714x10(-3) SH2(n=22, r=0.9042).

CONCLUSIONPlasma protein binding of cephalosporins is closely related with their lipophilicity and hydrogen- bonding potential. The plasma protein binding rate of cephalosporins can be predicted from their molecular weights and surface areas of hydrogen-bonding donors.

Algorithms ; Binding Sites ; Blood Proteins ; metabolism ; Cephalosporins ; chemistry ; metabolism ; Humans ; Hydrogen Bonding ; Molecular Weight ; Monte Carlo Method ; Protein Binding ; Regression Analysis

OBJECTIVETo compare the contents of resveratrol and polydatin in some materials of Polygonum cuspidatum from various sources, so to screen and obtain the suitable cultures for the following metabolism regulation study.

METHODRP-HPLC method was applied to simultaneously assay resveratrol and polydatin in different samples.

RESULTBy the modified methods of extraction and determination, large amount of materials were screened. The results indicated that the contents of resveratrol and polydatin in root and rhizome were evidently higher than those in the leave and stems. The content of polydatin in the seedlings cultured indoor for three months was 1.27% and showed a 1.25-time increse than that in the wild plants, while the content of resveratrol (0.401%) approached that in the wild plants. Both of resveratrol and polydatin could be examined from different tissue cultures of P. cuspidatum, such as the sterile seedlings, callus, suspended cells and hairy roots, and the levels of them were closely related to the growth speed, physiological status and developmental phase. Hairy roots had the highest potentiality in several tested cultures and the increase rate of dry weight was 8.29 when cultured in vitro for 30 days, and showed a 8.4-fold and a 192.8-fold increase compared with those of natural roots and suspended cells, respectively. The content of polydatin in the hairy roots was up to 0.037% and that of resveratrol was 0.007%.

CONCLUSIONThe established analysis method is rapid, simple and accurate, especially adapted to the simultaneous determination of resveratrol and polydatin in massive biological samples. Hairy-root cultures have the superiority among the tested materials of P. cuspidatum and are suitable for the large-scale biomass and consistent production of efficient constituents.

Biomass ; Chromatography, High Pressure Liquid ; methods ; Fallopia japonica ; chemistry ; growth & development ; Glucosides ; analysis ; Plant Leaves ; chemistry ; growth & development ; Plant Roots ; chemistry ; growth & development ; Plant Stems ; chemistry ; growth & development ; Plants, Medicinal ; chemistry ; growth & development ; Reproducibility of Results ; Rhizome ; chemistry ; growth & development ; Seedlings ; chemistry ; growth & development ; Stilbenes ; analysis ; Tissue Culture Techniques ; methods

Hepatitis B virus (HBV) represents a significant global public health challenge. Despite the availability of several approved drugs for hepatitis B treatment, the persistence of covalently closed circular DNA (cccDNA) renders HBV eradication elusive, thereby leading to disease relapse after drug withdrawal. This paper reviews the regulatory mechanisms of cccDNA formation, transcription and replication, and summarizes the research progress of related small molecule regulators from the perspective of medicinal chemistry.

OBJECTIVETo assess protein and mRNA expression levels of heparanase and basic fibroblast growth factor (bFGF) genes in human non-small cell lung cancer (NSCLC) and their roles in tumor invasion, metastasis and prognosis.

METHODSA total of 115 paraffin-embedded and 45 fresh-frozen tissue specimens of NSCLC were studied by immunohistochemistry, Western Blot and in situ hybridization to evaluate the protein and mRNA expression status of heparanase and bFGF genes. The data was analyzed by SPSS statistical software.

RESULTSBoth human heparanase and bFGF were highly expressed in NSCLC cells, in contrast to none or a low expression in normal lung tissue. Expression of heparanase also showed a significantly higher than that in the normal tissue by Western blot (P = 0.041). Immunohistochemistry showed that heparanase expression was both cytoplasmic and membranous. The agreement between heparanase and bFGF was significant. A significant correlation was found between the expression of either protein and TNM stage, vascular invasion, lymphatic metastasis and microvascular density (MVD). Co-expression of the two proteins demonstrated an even higher correlation with the tumor stage and MVD. In addition, expression of bFGF correlated with tumor cell differentiation. Data of a multivariate analysis indicated that tumor cell differentiation, vascular invasion, lymphatic metastasis and expression of bFGF were identified as significant prognostic parameters.

CONCLUSIONSBoth heparanase and bFGF may play important roles in tumor angiogenesis, metastasis, and prognosis of NSCLC.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; enzymology ; metabolism ; pathology ; Cell Differentiation ; Female ; Fibroblast Growth Factor 2 ; metabolism ; Glucuronidase ; metabolism ; Humans ; Lung Neoplasms ; enzymology ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Microcirculation ; pathology ; Middle Aged ; Neoplasm Staging ; Neovascularization, Pathologic ; Prognosis ; Survival Rate

Adult ; CD8-Positive T-Lymphocytes ; immunology ; Case-Control Studies ; Female ; Hepatitis B, Chronic ; immunology ; metabolism ; pathology ; Humans ; Liver ; immunology ; pathology ; Male ; Middle Aged ; T-Cell Antigen Receptor Specificity ; Young Adult

OBJECTIVE: To explore the change of content of minor elements and its biological implication in apoptotic processes. METHODS: The content of minor elements of apoptotic cells from breast cancer induced by anti-cancer drugs was quantitatively analysed with synchronous radiation X-ray fluorescence. RESULTS: Seven kinds of minor elements including Ti, Cr, Fe, Cu, Zn, Ga and Ge as well as five major elements P, S, Ca, Cl and K were detected in the apoptotic and control cells. The content of elements Zn and P in apoptotic cells after 48 h treatment with taxol and colchicine was significantly increased higher than that in the control cells P<0.05). The content of element Fe in 48 h treatment with taxol was significantly decreased lower than that in the control cells P<0.05). The same trend of change of elements was observed during the process of apoptotic cells death induced with VP-16 or cycloheximide. CONCLUSION: This results suggest that the elements Zn, Fe and P should be involved in apoptosis induced by anti-cancer drugs.