Determination of metformin in diabetic rat plasma by an improved ion-pair high-performance liquid chromatography: application to a pharmacokinetic study

An efficient and sensitive ion-pair HPLC-UV method using atenolol as internal standard （IS） was developed and validated for the determination of metformin in the plasma of diabetic rats. Plasma samples were deproteinated with 10% （v/v） perchloric acid. Separation was achieved on a UltimateTM AQ-C18 column （250 mm×4.6 mm, 5 μm） with a mobile phase （pH 5.05） composed of acetonitrile-water （31：69, v/v, containing 0.002 M sodium dodecyl sulfate, 0.0125 M potassium dihydrogen phosphate, 0.015 M triethylamine） at a flow rate of 1.0 mL/min. The calibration curve was linear （r〉0.994） between 7.5 and 4000 ng/mL. The lower limit of quantification （LLOQ） was 7.5 ng/mL. The precision was validated and the relative standard deviation was in the range of 1.87% to 15.70%; the accuracy was between 93.98%-106.89%. The mean recoveries were 95.40% and 95.31% for metformin and IS, respectively. The relative error （RE） of stability at different storage conditions was within ±9.00%. This method was used to determine the concentration-time profile of metformin in diabetic rat plasma following an oral administration of metformin at the dose of 10 mg/kg. Our results indicated that ion-pair HPLC-UV method using UltimateTM AQ-C18 column was effective for the pharmacokinetic studies of high polarity compounds like metformin.

Triterpenoids from the stems of Casearia velutina Bl.

To investigate the chemical components from the stems of Casearia velutina Bl.,the constituents were isolated by repeated chromatography with silica gel,Sephadex LH-20,and ODS columns.The structures were elucidated by spectroscopic analysis.Eleven triterpenoids and its glycosides were isolated from the crude extract of C.velutina,and their structures were identified as friedelin-2,3-lactone（1）,friedelane（2）,epifriedelanol（3）,friedelin（4）,2α,3α,19α-trihydroxy-urs-12-en-28-oic acid（5）,2α,3β,19α-trihydroxy-urs-12-en-28-oic acid（6）,2α,3α,23-trihydroxy-urs-12-en-28-oic acid（7）,2α,3α,23-trihydroxy-olean-12-en-28-oic acid（8）,2α,3α,19α,23-tetrahydroxy-urs-12-en-28-oic acid（9）,2α,3α,19α,23-tetrahydroxy-urs-12-en-28-oic acid-28-O-β-D-glucopyranosyl ester（10）,and 3β,19α-dihydroxy-urs-12-en-28-oic acid 3-O-α-L-arabinopyranoside（11）.All the compounds described above were isolated from this species for the first time.Compound 1 is a rarely occurred seco-friedelolactone in Flacourtiaceae.

Chemical constituents from Aquilaria sinensis(Lour.) Gilg

To investigate the chemical constituents of the stems ofAquilaria sinensis （Lour.） Gilg, the separation and purification were performed by solvent extraction, repeated chromatography on silica gel, Sephadex LH-20 and prep-HPLC. The structures were determined by spectrum analysis. Thirteen known compounds were isolated and their structures were identified as justicidin A （1）, justidin F （2）, ciwujiatone （3）, （＋） syringaresinol （4）, syringaresinol-4,4＇-di-O-13-D-glucopyranoside （5）, syringaresinol-4＂O-β-D- glucopyranoside （6）, curuilignan D （7）, syringin （8）, koaburaside （9）, 3,4,5-trimethoxyphenyl-l-O-β-D-glucopyranoside （10）, 3,4,5-trimethoxyphenyl-l-O-13-D-apiofuranosyl-（1 ＂→6＇） glucopyranoside （11）, 7-ketositosterol （12）, 7-oxo-5,6-dihydrostigmasterol （13）. All the compounds described above were isolated from genus Aquilaria for the first time.

Cheminformatics analysis of the Chinese National Compound Library of Peking University

The Chinese National Compound Library of Peking University （PKU-CNCL） is a new high-throughput screening collection aimed at driving precompetitive drug discovery and target validation, and is one of satellite libraries of the Chinese National Compound Library （CNCL）. It is a chemical database containing binding, functional, and ADMET information for a large number of drug-like bioactive compounds. These data are manually abstracted from the primary literature on a regular basis, and further curated and standardized to maximize their quality and utility across a wide range of chemical biology and drug-discovery research problems. Currently, the database contains 54 000 bioactivity measurements for more than 100 000 compounds. Access, data downloads, and web services are available at： http：//www.pkucncl.cn.

Anti-tumor efficiency of NGR-modified PEG-PLGA micelles containing paclitaxel:in vitro and in vivo

In the present study, we prepared novel NGR-modified PEG-PLGA polymeric micelles containing paclitaxel （NGR- PM-PTX） in order to evaluate their potential targeting to aminopeptidase N receptors expressed on tumor endothelial cells and the tumor cell surface and its anti-tumor activity in vitro and in vivo. NGR-PM-PTX was prepared by thin-film hydration method. The in vitro targeting characteristics of NGR-modified PM on HUVEC （human umbilical vein endothelial cells）, HT1080 （human fibrosarcoma cells） and MCF-7 （human breast adenocarcinoma cells） were then investigated. The anti-tumor activity of NGR-PM-PTX was evaluated in HT1080 tumor-bearing mice in vivo. The targeting activity of the NGR-modified PM was demonstrated by flow cytometry and confocal microscopy in vitro. NGR-PM-PTX also produced marked anti-tumor activity to HTI080 tumor-beating mice in vivo.

Study of the prodrugs of peptide aldehydes as proteasome inhibitors

To improve the stability of peptide aldehyde proteasome inhibitors, four peptide cycloacetal derivatives and two peptide heterocycle compounds were designed and synthesized. Their proteasome inhibition and in vitro anticancer activities were evaluated. The four peptide cycloacetal derivatives did not showed any activities, which demonstrated that this kind of cycloacetal derivatives might be suitable as prodrugs. The two peptide heterocycle compounds were found to show obvious activities at both enzyme and cell levels. These results provide us a new clue for the modification of peptide aldehyde proteasome inhibitors.