OBJECTIVE To develop a sensitive and rapid HPLC-MS/MS method for the determination of losartan potassium and E-3174 in human plasma. METHODS The plasma samples were extracted with methyl tert-butyl ether (MTBE) after addition of internal standard and acetic acid, and then analyzed with API 3000 LC-MS/MS system. The analytical column was SHISEIDO, CAPCELL PAK C₁₈ MGⅡ(2.0 mm×50 mm, 5 μm) and the column temperature was room temperature. The mobile phase was composed of 0.1% formic acid in water (containing 5 mmol·L^-1 ammonium acetate) -0.1% formic acid in acetonitrile (20∶80) and the flow rate was 0.85 mL·min^-1. Detection was performed with multiple reactions monitoring (MRM) using positive electrospray ionization (ESI). RESULTS The calibration curves were linear over the concentration ranges of 10.10-2 525 ng·mL^-1 for losartan potassium and 9.820-2 455 ng·mL^-1 for E-3174, respectively. The lower-limit-of-quantifications were 10.10 ng·mL^-1 for losartan potassium and 9.820 ng·mL^-1 for E-3174, respectively. Inter- and intra-day precisions were less than 9.22% and accuracy was within 93.56%-102.88%. Extraction recoveries were around 70% and the analytes were proved to be stable. Total run time of an analyte was only 2.5 min. The relative bioavailabilities of the two preparations were 96.5% for losartan potassium and 110.0% for E-3174. These two losartan potassium preparations were bioequivalent. CONCLUSION This method is rapid, sensitive, specific and applicable to the pharmacokinetic study in human and bioequivalence study of losartan potassium.

To investigate the best method for preparing NGR-SWCNTs-paclitaxel and observe its targeting efficency. METHODS SWCNTs-paclitaxel was prepared by solution mixing, and then conjugated with NGR to obtain a novel paclitaxel delivery system:NGR-SWCNTs-paclitaxel. Taking loading efficiency and encapsulate efficiency as index,studied the influential factors of the preparation of NGR-SWCNTs-paclitaxel by surfactant、times and frequency of probe sonography, quantity of carbon nano tube. The drug concentration in different tissue were detected by high performance liquid chromatography(HPLC).The targeting efficiency were used to evaluate the tissue targeting of NGR-SWCNTs-paclitaxel, SWCNTs-paclitaxel and paclitaxel.RESULTS SWCNTs-paclitaxel was prepared by SWCNTs-paclitaxel was 1∶2; Poloxamer188-phenylalanine was 7∶3;probe sonography 600 W,15 times. SWCNTs-paclitaxel conjugated with NGR formed NGR-SWCNTs-paclitaxel . Its loading efficiency was (83.9±2.7)% and encapsulate efficiency was (69.3±1.5)%. The Zeta potential was(-22.6±1.5)mV, partical size was about(182.1±2.4)nm. The AUC of NGR-SWCNTs-paclitaxel and SWCNTs-paclitaxel in mice slpeen、liver、lung and tumor were increased obviously compared with paclitaxel(P<0.05,P<0.01).The targeting efficiency of SWCNTs-paclitaxel and NGR-SWCNTs-paclitaxel in heart and kidney were decreased(P<0.05), and in tumor the targeting efficiency was 6.78% and 21.33% separately, the difference was significantly(P<0.01). CONCLUSION The preparation of NGR-SWCNTs- paclitaxel was practicable by solution mixing. The loading efficiency and encapsulate efficiency of NGR-SWCNTs-paclitaxel are higher. NGR-SWCNTs-paclitaxel can enhance tumor targeting of paclitaxel obviously.

OBJECTIVE To discuss the availability of evaluation on pharmacokinetics for the system of complicated components by studying the in vivo blood dynamic change of Beagle dogs from Yangxue injection in interval time. METHODS Yangxue injection were administered to dogs by intravenous infusion, plasma samples were collected at different times and treated with methanol to precipitate protein.Area under the absorbance-wavelength curve(AUAWC) and total concentration of sodium ferulate, tetramethylpyrazine hydrochloride and tanshinol sodium in plasma were obtained after a full ultraviolet-visible spectrum scan to samples from 200 to 350 nm wavelength. Meanwhile, individual concentrations of sodium ferulate, tetramethylpyrazine hydrochloride and tanshinol sodium in plasma were determined by HPLC method. The pharmacokinetic parameters by the method of AUAWC and HPLC were obtained after processed with 3P97 procedure from Chinese Pharmacology Institute. RESULTS To Yangxue injection with multicomponent, the former appeared to have a two-compartment model in the Beagle dogs, with pharmacokinetics′ parameters c₀ 84.94 μg·mL^-1, elimination half-life (t_1/2β) 46.94 min and area under concentration versus time (AUC) 3 227.77 min·μg·mL^-1. The results of the latter by HPLC demonstrated that sodium ferulate and tetramethylpyrazine hydrochloride appeared to have a one-compartment model in the Beagle dogs, c₀ were 37.02 and 0.54 μg·mL^-1,t_1/2 were 26.24 and 32.35 min,AUC were 1 406.75 and 20.50 μg·min·mL^-1. Tanshinol sodium appeared to have a two-compartment model in the Beagle dogs, with pharmacokinetics’ parameters c₀ 48.48 μg·mL^-1, elimination half-life (t_1/2β) 59.21 min and AUC 1 842.06 μg·min·mL^-1.The results indicated that the total components concentration in plasma and AUC got through the way of AUAWC were greater than that of a single component by HPLC. CONCLUSION The pharmacokinetic characteristics of Yangxue injection in Beagle dogs is shown by the method of AUAWC, which will bring a feasible idea and pathway to pharmacokinetics’ studies of chemicals compound, traditional Chinese medicine with multicomponents and complicated compound of traditional Chinese medicine under the combination between the method of AUAWC and HPLC.

OBJECTIVE To study variation of total flavonoids from nine different Bupleurum chinense introduced of different ground parts of different organs in different growth period, and explore the best harvest period and the optimal varieties. METHODS The extraction conditions were optimized by microwave assisted method,UV-visible spectropholometry was used to determine the contents of total flavonoids. RESULTS The optimum extraction conditions:the concentration of ethanol was 80%, each microwave time 40 s, microwave 10 times; the content of total flavonoids was difference in different growth period, fluctuated trend. The flower was the highest, with an average of 7.59% in the range of 4.65%-16.75%,the content of total flavonoids in nutrition growth phase:leaf>stem, in flowering stage:flower>leaf>stem; in fruiting stage:the content of Gansu Longxi, Liaoning Shenyang, Shandong Heze and Hebei Anguo Bupleurum:fruit >leaf> stem, other Bupleurum:leaf >stem>fruit;The higher the content of total flavonoids was in the flowering and fruiting of nine different Bupleurum chinense introduced, Gansu Longxi Bupleurum (flowering stage) was the highest, up to 27.41%. CONCLUSION It is suggested that harvested in the flowering or fruiting stage,and carried on the comprehensive development and utilization.

OBJECTIVE To include the water-soluble drug catalpol by novel vesicle formed by polyethylene glycol (PEG, Mn=2 000) and beta-cyclodextrin (β-CD) based on the principle of molecular self-assembly. METHODS The morphologies and structures of the vesicles were characterized by means of transmission electron microscopy (TEM), Zeta potential analyzer, and laser particle size instrument. The water-soluble drug catalpol was included in the novel vesicle and the drug inclusion rate was determined by UV-Vis spectrophotometry.RESULTS The drug loaded niosomes were prepared successfully. The particle size distribution of the niosomes was around 110 nm, which was close to the level of nanometer vesicles; the Zeta potential was about -19 mV, illustrating the vesicle stability was good. In addition, the particle size and Zeta potential changed along with the change of vesicle concentration and pH value. The drug loading rate of the vesicle was around 52%. CONCLUSION This study establishes a new characterization system for drug loaded vesicles, and provides a reference for clusion of water soluble medicines.

Lipoprotein- associated phospholipase A2 (Lp- PLA2) is a member of phospholipases superfamily which can hydrolyze oxidative phospholipid in low density lipoprotein (LDL), and produce two proinflammatory mediators including lysophosphatidylcholine (lysoPC) and oxidized free fatty acid. Thus, Lp- PLA2 is believed to mediate the inflammatory processes that lead to atherogenesis. Recent studies indicated that Lp- PLA2 acts as a new marker in the inflammatory process and is an independent predictor of the cardiovascular diseases. Many Lp- PLA2- targeted inhibitors have been designed to deal with the key enzyme involving in atherosclerosis. Darapladib is the specific inhibitor which is closest to the market among the rest and is drawn wide attention as an emerging therapy for atherosclerosis, and the clinical phase Ⅲ trials have been completed. Numerous experiments have confirmed that Darapladib could decrease the activity of Lp- PLA2, reduce inflammatory reaction and disrupt the development of atherosclerosis. In this paper, the authors summarized the mechanism of Lp- PLA2 and Darapladib in atherosclerosis, and the recent advances on the pharmacodynamics of Darapladib in recent years.

OBJECTIVE To develop an HPLC-MS/MS method coupled with EZ:faast^TM amino acid analysis kits for the determination of glutamine in rat plasma for the pharmacokinetic study in rats.METHODS The plasma samples were prepared by EZ:faast^TM amino acid analysis kits and then analyzed with API 3000 HPLC-MS/MS system. The analytical column was Phenomenex EZ:faast 4 μ AAA-MS(4 micron, 3.00 mm×250 mm) and the column temperature was 20 ℃. The mobile phase was composed of 0.2% formic acid aqueous solution(containing 5 mmol·L^-1 ammonium acetate)-methanol and eluted gradiently at a flow rate of 0.4 mL·min^-1. The detection was performed with multiple reactions monitoring(MRM) using positive electrospray ionization(ESI). RESULTS The calibration curve for glutamine was linear over the concentration range of 3.003-150.2 μg·mL^-1(r=0.996 6). The lower limit of quantification was 3.003 μg·mL^-1. The inter- and intra-day RSDs were less than 15% and the accuracy was within 85%-115%. The extraction recoveries were around 90%, and glutamine was proved to be stable under different circumstances.CONCLUSION This method is specific, sensitive, and accurate, and the sample preparation procedure is simple, rapid, and suitable for the pharmacokinetic study of glutamine in rats.

OBJECTIVE To develop an HPLC method for the determination of arctigenin in rat plasma and study the pharmacokinetics of arctigenin nanoemulsion. METHODS The plasma samples were extracted by ethyl acetate. The determination was carried out on an Agilent C₁₈ column (4.6 mm×250 mm, 5 μm) with the mobile phase consisting of methanol-0.2% phosphoric acid (52∶48, V/V) and the UV detection wavelength was set at 280 nm. Quercetin was selected as internal standard. Arctigenin nanoemulsion was administered to rats by intravenous injection at a dose of 4 mg·kg^-1. The plasma concentration of arctigenin at different time points was determined by the established HPLC method. The pharmacokinetic parameters were processed by DAS2.1 software. RESULTS The calibration curve of arctigenin had acceptable linearity in the range of 0.1-10 mg·L^-1 in rat plasma(r=0.999 2). The lower limit of quantitation(LLOQ)was estimated to be 0.1 mg·L^-1and the lower limit of detection (LLOD)was estimated to be 0.03 mg·L^-1. The mean extraction recovery rates of arctigenin QC samples at low, medium and high concentration levels were all above 85%. The intra-day and inter-day precisions were less than 6%. The pharmacokinetics of arctigenin in rats after intravenous injection were fitted to a two-compartment model and the half-lives of α phase and β phase were (0.134±0.085) and (1.471±0.164) h, respectively. CONCLUSION The HPLC method is simple, rapid and accurate. It can be used for monitoring the plasma concentration of arctigenin and its pharmacokinetic study. After intravenous administration of arctigenin nanoemulsion, arctigenin is rapidly distributed into tissues,but the elimination is slow.

OBJECTIVE To investigate the flavonoid glycosides in Clematis connata DC. METHODS Colum chromatography with different materials, such as RP-18, Sephadex LH-20 and silica gel, and semi preparative high performance liquid chromatography were used to isolate and purify the chemical constituents. Their structures were identified by spectroscopic analysis.RESULTS Eleven flavonoid glycosides were isolated and identified as kaempferol-3-O-β-D-glucopyranosyl methyl ester(1), isovitexin(2), kaempferol-3-O-β-D-glucopyranoside-7-α-L-rhamnopyranoside(3), kaempferol-3-O-α-L-rhamnopyranoside-7-α-L-rhamnopyranoside(4), kaempferol-3-O-α-L-(4-O-acetyl) rhamnopyranoside-7-α-L-rhamnopyranoside(5), kaempferol-3-O-(2-β-D-glucopyranosyl)-α-L-rhamnopyranoside-7-O-α-L-rhamnopyranoside(6), genistein-7-O-β-D-apiofuranosyl-(1→6)-O-β-D-glucopyranoside(7), lanceolarin(8), quercetin-3-O-β-D-(6″-n-butyl) glucuronide(9), quercetin-3-O-β-D-glucopyranosyl methyl ester(10), and isoorientin(11). CONCLUSION Compounds 1-11 are isolated from Clematis connata DC for the first time.

Non-standardized planting, breeding, harvest and original process of Chinese herbal medicines, illegal dye addition and weight gain of Chinese medicine decoction pieces, and illegal production and business of counterfeit decoction pieces, all these seriously influence the quality and safety of Chinese medicinal materials and decoction pieces. In the year of 2013, a market quality surveillance project of Chinese medicinal materials and decoction pieces was carried out by the China Food and Drug Administration. This paper is a summary and analysis of the project, with the hope to reflect current situation of the quality of Chinese herbal medicines and decoction pieces.

OBJECTIVE To learn from innovative strategies for pharmacy education in pharmacy practice at home and abroad, and provide references for the improvement pharmacy education management in China. METHODS Innovative strategies for pharmacy education were retrieved and analyzed. RESULTS For the processes pharmacy education, analytic reasoning skills, intra-lecture assessment and adaptive teaching were used. For curriculum, differences among countries were compared and innovation aspects were pointed out. For information technology, online global pharmacy education community,virtual pharmacy and educational virtual resource were explored. For the impact pharmacy education innovation on clinical practice, influence on health related quality life in HIV/AIDS patients and an inter-disciplinary collaborative learning were introduced. CONCLUSION More research on the reform pharmacy education is warranted to better pharmacists′ role in the clinical practice.

OBJECTIVE To evaluate the effectiveness and safety of metaraminol in maintaining hemodynamics during anaesthesia. METHODS Cochrane library, Pubmed, Embase, CBM, CNKI, VIP and Wanfang Database were searched. Randomized controlled trials(RCT) of metaraminol vs placebo or ephedrine in maintaining hemodynamics during anaesthesia were selected, and quality evaluation and Meta analysis were performed. RESULTS Ten RCTs were selected. The efficacy of metaraminol in maintaining hemodynamics during anaesthesia was better than placebo, it showed significant differences between the two groups in the incidence of hypotension and in the reduction of SAP , but no significant difference in the change of heart rate . There were no significant difference between metaraminol and ephedrine in the incidence of hypotension , the reduction of SAP and the change of heart rate . CONCLUSION The effect of metaraminol on maintaining hemodynamics during anaesthesia is equivalent to that of ephedrine; meanwhile metaraminol has fewer adverse effects than ephedrine.

OBJECTIVE To assess the effectiveness and safety of letrozole (LE) for ovulation induction in women with PCOS. METHODS Pubmed, Embase, CNKI, and the Cochrane Library were searched. Randomized controlled trials of letrozole for ovulation induction in women with PCOS were collected. The quality of the retrieved trials was assessed, and meta-analyses were conducted using RevMan software 5.1. RESULTS Six RCTs were included, all of which were published in English. The RESULTS of Meta-analyses showed that there were no significant differences between letrozole and clomiphene Citrate in pregnancy rate, ovulation rate, miscarriage rate and adverse event incidence,（1.15[0.86，1.54]，1.11[0.91，1.34]，1.45[0.52，4.08]，0, [-0.01，0.01]）. For the patients with BMI＜30, letrozole was more effective than clomiphene citrate in pregnancy rate [RR=1.64, 95%CI（1.08，2.50）]. CONCLUSION Letrozole can be considered as first-line treatment for ovulation induction for patients with BMI＜30. According to the guideline, the lifestyle should be modified before treatment for patients with BMI＞30. Due to insufficient evidence available in the literature, more large scale, good-designed RCTs are needed to confirm whether letrozole can be used as first-line drug.

OBJECTIVE To research the cognition, attitude and practice, the present situation and expectation obstetric medical staff on pharmaceutical care, provide the basis for establishing pharmaceutical service pathway for pregnant and delivery women. METHODS Design questionnaire refer to literature and based on our actual situation, questions include individual choice and multiple choice, one score for every choice. The 202 questionnaires are sent to the 6 inpatient and 2 outpatient wards, the data were analyzed by SPSS20.0 statistical software. RESULTS Response rate is 100%, and the effective rate is 99.5%. Medical staffs welcome pharmaceutical service, the cognitive score is high, at the same time, they think there are some difficulties need to be solved, which include the pharmacists′ knowledge, skills and attitude the leaders, etc. The service forms include printed drug and disease information, pharmacy information query machine in hospital. The service contents mainly include counseling and guidance, adverse drug reaction monitoring, drug related problem analysis, pharmaceutical education and individualized dosage project. CONCLUSION Obstetric medical staff provides important policy support on pharmaceutical service pathway including the opportune moment, forms and contents.

OBJECTIVE To evaluate bioequivalence of two paracetamol, dextromethorphan hydrochloride, pseudoephedrine hydrochloride and diphenhydramine hydrochloride tablets in healthy volunteers. METHODS In randomized crossover design, a single dose of test formula and reference formula was given to 20 healthy male volunteers. Dextrorphan, pseudoephedrine and diphenhydramine were measured by LC-MS/MS, paracetamol by HPLC-UV. RESULTS After a single oral administration test formula and reference formula, the main pharmacokinetic parameters of paracetamol were as follows:ρ_max (6.16±1.24) and (6.04±1.03) mg·L-1, t_max (1.31±0.69) and (1.50±0.70)h，AUC_{0-16 h} (29.17±6.67) and (28.76±6.29 )mg·h·L-1. Pharmacokinetic parameters of pseudoephedrine were as follows:ρ_max (210.0±30.3) and (214.6±35.7)μg·L-1，t_max (2.33±1.08) and (2.23±1.19)h，AUC_{0-24 h} (1 887.4±364.3) and (1 936.8±444.3)μg·h·L-1. Pharmacokinetic parameters of diphenhydramine were as follows: ρ_max (84.4±24.6) and (92.2±29.2)μg·L-1，t_max (2.75±1.11 ) and (2.98±1.06)h，AUC_{0-36 h} (819.2±284.7) and (937.5±391.4) μg·h·L-1. Pharmacokinetic parameters of dextrorphan were as follows: ρ_max (6.63±2.90) and (6.00±2.15) μg·L-1，t_max (2.73±0.92) and (2.58±1.05)h，AUC_{0-24 h} (42.79±13.02) and (40.24±11.92) μg·h·L-1.The relative bioavailability of paracetamol, pseudoephedrine, diphenhydramine and dextromethorphan were (99.1±9.6)%, (102.7±13.5)%, (114.3±25.3)% and (95.6±17.3)%, respectively. CONCLUSION The results of statistical analysis demonstrated that the two preparations were bioequivalent.

Novel coronavirus 2019 (SARS-CoV-2) infection outbreak has occurred in Wuhan since December 2019.Cytokine storm (inflammatory factor storm)was suggested to be involved in the sudden deterioration of some SARS-CoV-2 infectors in the recent reports.However, no medicine was specific to the treatment of cytokine storm so far. This paper summarized the mechanism and potential therapeutic drugs of cytokine storm based on literature review and analysis, so as to provide references for the treatment of SARS-CoV-2.

OBJECTIVE To discuss the effects of Lianhua Qingwen granules plus arbidol on treatment of mild corona virus disease-19 (COVID-19). METHODS A total of 295 COVID-19 patients (2020.2.17-2020.3.6) in Wuhan Third Hospital were chosen and randomly assigned to control group (n=148) and observation group (n=147). The control group orally took arbidol and the observation group took Lianhua Qingwen granules and arbidol. TCM symptom scores, white blood count (WBC), lymphocyte count (LYM), C-reactive protein (CRP), procalcitonin (PCT) and chest CT review conditions were compared. RESULTS Total effective rate in the observation group was significantly higher than control group ((80.95% vs. 64.86%); severe transfer rate in the observation group was lower than control group (14.29% vs. 23.65%) (P＜0.05); after 7 d of treatment, TCM syndromes like fever, weakness, cough, throat dryness and sore and chest discomfort, CRP and PCT levels in the observation group were significantly lower than control group (P＜0.05); WBC and LYM levels in the observation group were significantly higher than control group (P＜0.05); based on CT review, effective cure rate in the observation group (69.39%) and control group (62.84%) was not significantly different (P＞0.05). Both of groups had no serious adverse reactions. CONCLUSION Lianhua Qingwen granules combined with arbidol can relieve the clinical symptoms, adjust the inflammatory factors, increase the curative effects and reduce the severe transfer rate.

Beginning at the end of 2019, corona virus disease 2019(COVID-19) caused by sevare acute respiratory syndrome coronavirus(SARS-CoV-2) appeared in Wuhan, China, and spread rapidly across the country. Prior to this, there had been two outbreaks in the world that caused serious consequences by different coronaviruses: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). This article introduces the structure and classification of coronaviruses, discusses the origin, virological characteristics, and epidemiological overview of three coronaviruses-SARS-CoV, MERS-CoV, and SARS-CoV-2, and reviews the drugs that are currently on the market and are being developed to treat coronavirus infections, in order to explain the characteristics of coronavirus and provide new ideas for the prevention and control of 2019-nCoV and new coronavirus.

OBJECTIVE To explore the significance of stability evaluation of monoclonal antibodies (mAbs), an important part of druggability of mAbs, from the aspects of structural stability, colloidal stability and weak intermolecular interaction. METHODS Taking trastuzumab, rituximab and bevacizumab as examples, the stability characteristics of the three mAbs were explored from different aspects, thus to demonstrate various dimensions of stability evaluation of mAbs. Firstly, the structural stability of antibody molecules was evaluated by detecting the melting temperature (T_m) through intrinsic fluorescence (IF). Secondly, static light scattering technique (SLS) was used to predict the colloidal stability of mAbs. Subsequently, isothermal stability tests (60 ℃, 48 h) were used to monitor the stability performance of the samples in real time. Lastly, dynamic light scattering technique (DLS) was used to predict protein aggregation tendency from the point of weak intermolecular interaction of dissolved proteins. RESULTS IF detection showed that the first melting temperature (T_m1) of the three mAbs were all above 65 ℃, indicating that their structures were stable. SLS detection showed that trastuzumab had the best colloidal stability since no obvious aggregation signal was detected at 95 ℃, while rituximab and bevacizumab showed obvious aggregation at about 70 ℃. The isothermal stability test also showed similar results. The application of DLS techniques showed that the second virial coefficient (B₂₂) and diffusion interaction coefficient (K_D) of trastuzumab were positive (3.19×10^-3, 65.46), indicating better long term colloidal stability, rituximab was suboptimal, while the B₂₂ and K_D of bevacizumab were both negative (-1.44×10^-4,-6.46), suggesting that the molecules were prone to be self-associated. CONCLUSION In this paper, the contents, levels and depth of the stability evaluation of mAbs are characterized by various techniques and discussed from multi-aspects, which provides reference for antibody molecular screening, formulation optimization, different combinations between antibody molecules and formulations, stability evaluation and so on.