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Journal of Pharmaceutical Analysis 2017年第3期7卷 163-169页

作者： Jaivik V.shah Priyanka A.shah Priya V.shah Mallika sanyal Pranav s.shrivastav Department of Chemistry School of Sciences Gujarat University Department of pharmacy M.S.University Department of Chemistry St.Xavier's College

A sensitive and rapid liquid chromatography-tandem mass spectrometry(LC–Ms/Ms) method has been developed for the simultaneous determination of lisinopril(LIs) and hydrochlorothiazide(HCTZ) in human plasma using their labeled internal standards(Iss). sample pre-treatment involved solid phase extraction on Waters Oasis HLb cartridges using 100 μL of plasma, followed by liquid chromatography on Hypersil Gold C_(18)(50 mm×3.0 mm, 5 μm) column. The analytes were eluted within 2.0 min using acetonitrile-5.0 m M ammonium formate, p H 4.5(85:15, v/v) as the mobile phase. The analytes and Iss were analyzed in the negative ionization mode and quantified using multiple reaction monitoring. The method showed excellent linearity over the concentration range of 0.50–250.0 ng/m L for both the analytes. The intra-batch and inter-batch precision(% CV) was ≤5.26% and their extraction recoveries were in the range of 96.6%–103.1%. Matrix effect evaluated in terms of Is-normalized matrix factors ranged from 0.97 to 1.03 for both the analytes. The validated method was successfully applied to determine the plasma concentration of the drugs using 10 mg lisinopril and 12.5 mg hydrochlorothiazide fixed dose formulation in 18 healthy Indian volunteers.

关键词： Lisinopril Hydrochlorothiazide LC–Ms/Ms solid phase extraction Human plasma

Green synthesis of 1,2,4-thiadizoles from thioamides in water using molecular oxygen as an oxidant

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Chinese Chemical Letters 2014年第11期25卷 1499-1502页

作者： Jin-Wu Zhao Jing-Xiu Xu Xiu-Zhen Guo school of pharmacy Guangdong Medical College

We present here an efficient green process for the synthesis of 1,2,4-thiadiazoles via iodine-catalyzed,oxidative dimerization of thioamides in water using molecular oxygen as a terminal oxidant. Under the optimized reaction conditions, aryl thioamides produced 3,5-diaryl-1,2,4-thiadiazoles in good to excellent yields. Alkyl thioamides and substituted thioureas could also provide corresponding 1,2,4-thiadiazole products.

关键词： 1 2 4-Thiadizole Thioamide Water Oxygen

synthesis and physiochemical property evaluation of carbamate derivatives of scutellarin methyl ester

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Chinese Chemical Letters 2013年第4期24卷 338-340页

作者： Feng-Jie Jiang Xiao-Zhong Fu shan-Wu Wang Yong Huang Wen Zhou Ai-Min Wang Yong-Lin Wang school of pharmacy Guiyang Medical College

A series of carbamate prodrugs of scutellarin methyl ester （4a-4e） were prepared in the presence of bis（trichloromethyl） carbonate （bTC） with scutellarin methyl esters and L-amino acid tert-butyl ester hydrochloride as starting materials. In vitro stability and aqueous solubility of target compounds were evaluated. The results indicated that compounds 4d and 4e have higher solubility and in vitro stability than scutellarin respectively.

关键词： scutellarinbis(trichloromethyl) carbonatePhysiochemical property

Morroniside protects cultured human umbilical vein endothelial cells from damage by high ambient glucose

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Acta Pharmacologica sinica 2004年第4期25卷 14-17页

作者： Hui-qin XU2, Hai-ping HAO2, Xu ZHANG3,Yang PAN2 2college of pharmacy 3basicMedicine college, Nanjing Universityof Traditional ChineseMedicine, Nanjing 210029, China college of pharmacy basic Medicine college Nanjing University of Traditional Chinese Medicine

AIM: To determine whether morroniside, a compound in Cornus officinalis sieb et Zucc can prevent cultured human umbilical vein endothelial cells (HUVEC) from damage by high ambient glucose. METHODs: HUVEC was incubated in glucose, 5 or 30 mmol/L, either alone or in the presence of morroniside (final concentration 100, 10, and 1 μmol/L, respectively) for 48 h. The proliferation of HUVEC was quantified by MTT method; its cycle was analyzed by flow cytometry; morphological change was observed with fluorescence microscopy. REsULTs: survival of HUVEC cultured in high ambient glucose was significantly decreased when compared to that in normal concentration of glucose (Pbient glucose also lowered the rate of cells entering into s-phase, along with severe morphological damage. With the intervention of morroniside (final concentration 100 and 10 μmol/L), the cell survival was significantly recovered (Pspectively), accompanied with increased s-phase rate and less extent of morphological damage. CONCLUsION: Morroniside protected HUVEC against high ambi- ent glucose induced injury, which suggested that morroniside could exert a beneficial effect on preventing diabetic angiopathies.

关键词： morroniside umbilical veins endothelial cells diabetic angiopathies

simple synthesis of Magnetic Mesoporous Carbons with High surface Areas by soft-template Method

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Journal of Wuhan University of Technology(Materials science) 2013年第4期28卷 668-672页

作者：田勇 ZHONG Guoying 王秀芳 college of pharmacy Guangdong Pharmaceutical University

Magnetic Fe-containing ordered mesoporous carbons （Fe/OMCs） with high surface areas and pore volume were synthesized through a simple soft-template route, wherein phenolic resin was used as a carbon precursor, triblock copolymer F127 as a template agent, tetraethyl orthosilicate （TEOs） as a silica precursor and hydrated iron nitrate as an iron source. The effects of carbonization temperature, loading degree of TEOs on the structural parameters of these Fe/OMCs were evaluated by X-ray diffraction （XRD） and Nz sorption analysis. The ordering, the specific surface area and the total pore volumes increased with the increase of carbonization temperature from 600 to 850 ~C. And the specific surface area and the total pore volumes increased with the increase of TEOs loading.

关键词： mesoporous carbon iron synthesis

Application of an LC–Ms/Ms method for the analysis of amlodipine,valsartan and hydrochlorothiazide in polypill for a bioequivalence study

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Journal of Pharmaceutical Analysis 2017年第5期7卷 309-316页

作者： Jaivik V.shah Jignesh M.Parekh Priyanka A.shah Priya V.shah Mallika sanyal Pranav s.shrivastav Department of Chemistry School of Sciences Gujarat University Department of Chemistry St.Xavier's College Department of pharmacy M.S.University

A sensitive and selective method has been proposed for the simultaneous determination of amlodipine(AML),valsartan(VAL) and hydrochlorothiazide(HCTZ) in human plasma by liquid chromatography–tandem mass spectrometry(LC–Ms/Ms). The analytes and their deuterated analogs were quantitatively extracted from100 μL human plasma by solid phase extraction on Oasis HLb cartridges. The chromatographic separation of the analytes was achieved on a Chromolith RP18 e(100 mm × 4.6 mm) analytical column within 2.5 min. The resolution factor between AML and VAL, AML and HCTZ, and VAL and HCTZ was 2.9, 1.5 and 1.4, respectively,under isocratic conditions. The method was validated over a dynamic concentration range of 0.02–20.0 ng/m L for AML, 5.00–10,000 ng/m L for VAL and 0.20–200 ng/m L for HCTZ. Ion-suppression/enhancement effects were investigated by post-column infusion technique. The mean Is-normalized matrix factors for AML, VAL and HCTZ were 0.992, 0.994 and 0.998, respectively. The intra-batch and inter-batch precision(% CV) across quality control levels was ≤ 5.56% and the recovery was in the range of 93.4%–99.6% for all the analytes. The method was successfully applied to a bioequivalence study of 5 mg AML + 160 mg VAL + 12.5 mg HCTZ tablet formulation(test and reference) in 18 healthy Indian males under fasting. The mean log-transformed ratios of C max, AUC0–120 h and AUC0-inf and their 90% CIs were within 90.2%–102.1%. The assay reproducibility was demonstrated by reanalysis of 90 incurred samples.

关键词： Amlodipine Valsartan Hydrochlorothiazide LC–Ms/Ms Polypill bioequivalence

Novel triterpene saponins isolated from Clematis mandshurica and their inhibitory activities on NO production

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Chinese Journal of Natural Medicines 2018年第2期16卷 131-138页

作者： FU Qiang YANG Min MA Yu CHEN Jiang YUAN Hai-Mei college of pharmacy and biological Engineering Chengdu University

Four new triterpene saponins, mandshunosides F–I(1–4), together with five known compounds(5–9), were isolated from the roots and rhizomes of Clematis mandshurica. Their structures were elucidated on the basis of spectroscopic evidences and hydrolysis products. bisdesmosidic saponin(3–9) showed modest suppression of NO production with the inhibition ratios in the range of 51.3%– 64.6% at 50 μmol·L^(-1), whereas monodesmosidic saponins with a free carboxyl group at C-28(1 and 2) showed potent inhibitory activities with IC_(50) values being 12.7 and 8.3 μmol·L^(-1), respectively.

关键词： Clematis mandshurica Triterpene saponins Mandshunosides F—I NO production

selenium-layered nanoparticles serving for oral delivery of phytomedicines with hypoglycemic activity to synergistically potentiate the antidiabetic effect

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Acta Pharmaceutica sinica b 2019年第1期9卷 74-86页

作者： Wenji Deng Huan Wang baojian Wun Xingwang Zhang Department of Pharmaceutics College of Pharmacy Jinan University

Diabetes mellitus(DM) remains a great challenge in treatment due to pathological *** has been proven that phytomedicines and natural medicines have prominent antidiabetic effects. This work aimed to develop selenium-layered nanoparticles(seNPs) for oral delivery of mulberry leaf and Pueraria Lobata extracts(MPE), a group of phytomedicines with significant hypoglycemic activities, to achieve a synergic antidiabetic effect. MPE-loaded seNPs(MPE-seNPs) were prepared through a solvent diffusion/in situ reduction technique and characterized by particle size, ζ potential, morphology,entrapment efficiency(EE) and drug loading(DL). The resulting MPE-seNPs were 120 nm around in particle size with EE of 89.38% for rutin and 90.59% for puerarin, two marker components in MPE. MPEseNPs exhibited a slow drug release and good physiological stability in the simulated digestive *** oral administration, MPE-seNPs produced significant hypoglycemic effects both in the normal and diabetic rats. Ex vivo intestinal imaging and cellular examinations demonstrated that MPE-seNPs were provided with outstanding intestinal permeability and transepithelial transport aptness. It was also revealed that MPE-seNPs could alleviate the oxidative stress, improve the pancreatic function, and promote the glucose utilization by adipocytes. Our study provides new insight into the use of integrative nanomedicine containing phytomedicines and selenium for DM treatment.

关键词： Diabetes mellitus Phytomedicine bioavailability Hypoglycemic effect selenium nanoparticles

Quantification and pharmacokinetic study of tumor-targeting agent MHI148-clorgyline amide in mouse plasma using liquid chromatography-electrospray ionization tandem mass spectrometry

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Journal of Pharmaceutical Analysis 2018年第3期8卷 153-159页

作者： Zhijun Wang bogdan Z.Olenyuk Jean Chen shih Jeffrey Wang Center for Advancement of Drug Research and Evaluation College of Pharmacy Western University of Health Sciences Department of Pharmaceutical sciences College of Pharmacy Marshall B.Ketchum University Department of Pharmacology and Pharmaceutical sciences School of Pharmacy Department of Cell and Neurobiology Keck School of Medicine USC-Taiwan Center for Translational Research University of Southern California Department of Pharmaceutical sciences College of Pharmacy Western University of Health Sciences

A high-performance liquid chromatography-electrospray ionization tandem mass spectrometric （HPLC- EsI-Ms/Ms） method was developed for the quantification of MHl148-clorgyline amide （NMl-amide）, a novel tumor-targeting monoamine oxidase A inhibitor, in mouse plasma. The method was validated in terms of sensitivity, precision, accuracy, recovery and stability and then applied to a pharmacokinetic study of NMl-amide in mice following intravenous administration. NMl-amide together with the internal standard （Is）, MHI-148, was extracted by protein precipitation using acetonitrile. Multiple reaction monitoring was used for quantification of NMl-amide by detecting m/z transition of 491.2-361.9, and 685.3-258.2 for NMl-amide and the Is, respectively. The lower limit of quantification （LLOQ） of the HPLC- Ms/Ms method for NMl-amide was 0.005 μg/mL and the linear calibration curve was acquired with R2〉 0.99 in the concentration range of 0.005-2μg/mL. The intra- and inter-day precisions of the assay were assessed by percentage of the coefficient of variations, which was within 9.8% at LLOQ and 14.0% for other quality control samples, whereas the mean accuracy ranged from 86.8% to 113.2%. The samples were stable under storage and experimental conditions. This method was successfully applied to a pharmacokinetic study in mice following intravenous administration of 5 mg/kg NMl-amide.

关键词： MH1148-clorgyline HPLC Mass spectrometry Pharmacokinetics

Cancer chemoprevention through dietary avonoids: what's limiting?

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Chinese Journal of Cancer 2017年第10期36卷 455-467页

作者： Haneen Amawi Charles R. Ashby Jr Amit K. Tiwari Department of Pharmacology and systems Therapeutics College of Pharmacy and Pharmaceutical Sciences University of Toledo Toledo OH 43560USA Pharmaceutical sciences College of Pharmacy St. John’s UniversityQueens NY 11432 USA Department of Pharmacology and Experimental Therapeutics College of Pharmacy and Pharmaceutical Sciences University of Toledo Toledo OH 43614 USA

Flavonoids are polyphenols that are found in numerous edible plant species. Data obtained from preclinical and clinical studies suggest that specific flavonoids are chemo-preventive and cytotoxic against various cancers via a multitude of mechanisms. However, the clinical use of flavonoids is limited due to challenges associated with their e ective use, including(1) the isolation and purification of flavonoids from their natural resources;(2) demonstration of the e ects of flavonoids in reducing the risk of certain cancer, in tandem with the cost and time needed for epidemiological studies, and(3) numerous pharmacokinetic challenges(e.g., bioavailability, drug–drug interactions, and metabolic instability). Currently, numerous approaches are being used to surmount some of these challenges, thereby increasing the likelihood of flavonoids being used as chemo-preventive drugs in the clinic. In this review, we summarize the most important challenges and e orts that are being made to surmount these challenges.

关键词： Flavonoids Chemoprevention silybin silymarin Natural product drug development Pharmacokinetic challenges