OBJECTIVE: To Prepare amphiphilic hot-melt pressure sensitive adhesives (HMPSAs) and investigate the relationship among components, adhesion performance, drug release behavior of pH and transdermal permeation ability. METHODS: Based on the blend of styrene-isoprene-styrene (SIS) thermoplastic elastomer and acrylic resin Eudragit® EPO, following the addition of an appropriate amount of polyethylene glycol (PEG), mineral oil and C5 resin, the amphiphilic HMPSAs were prepared. The compatibility and micromorphology of SIS/EPO blends (SEBs) were analyzed with differential scanning calorimetry (DSC), atomic force microscopy (AFM) and scanning electron microscopy (SEM). The adhesive performance of HMPSAs was measured as 180° peeling strength and holding power. H-nuclear magnetic resonance spectrometer (H-NMR) was used to investigate the interaction between drugs and HMPSAs. The drug release behavior of arbutin and other five drugs were investigated, and the in vitro transdermal permeation was examined on mice's skin to compare the transdermal permeation ability of sinomenine hydrochloride and paeoniflorin in different HMPSAs. RESULTS: When the mass ratio of SIS to EPO was 1:2, bicontinuous structure was formed. The HMPSAs could maintain good adhesion performance, achieve continual release of both hydrophilic and lipophilic drugs and exhibit good transdermal permeation ability for hydrophilic drugs as well. Due to the protonation of EPO, the amphiphilic HMPSAs exhibited higher release rate and transdermal permeation ability in weakly acidic condition. CONCLUSION: The modified HMPSAs show good adhesive performance and pH sensitivity, so they are suitable for transdermal drug delivery system (TDDS).

OBJECTIVE: To design and prepare a novel polymeric micelles preparation for hydrophobic salinomycin (SAL), then evaluate the effects of SAL micelles on cancer stem cells in vitro. METHODS: SAL was entrapped into polymeric micelles constructed from amphiphilic diblock copolymer of poly (ethylene glycol)-block-poly (ε-caprolactone) (mPEG-b-PCL). Firstly, the process of preparing micelles and formulation composition were optimized. Then, the physicochemical properties such as particle size distribution, shape and surface morphology, stability and release rates of SAL-loaded micelles were studied. Finally, the side population (SP) cells were analyzed to evaluate the effects of SAL micelles on the MCF-7 cells. RESULTS: The optimal formulation of drug-loaded micelles was mPEG-b-PCL copolymers and SAL (20:1, w/w); the average particle size of SAL-loaded micelles was less than 30 nm, with narrow size distribution, uniform spherical shape and good stability. In vitro studies demonstrated that SAL-loaded micelles were able to decrease the proportion of SP cells. CONCLUSION: Polymeric micelles are capable of overcoming the poor solubility of SAL, and SAL-loaded micelles can selectively deplete breast cancer stem cells.

OBJECTIVE: To study the synthesis technique of poly(lactic-co-glycolic acid) (PLGA) via ring-opening polymerization. METHODS: Orthogonal experiments were carried out to optimize the synthesis conditions of PLGA under atmospheric condition. Three batches of repeated experiments were conducted to verify the technological conditions. RESULTS: The target product could be synthesized by using 0.03% stannous octoate and 0.02% lauryl alcohol reacted at 16°C for 10 h at a stir speed of 300 r·min-1. The ratio of glycolide and lactide was determined to be 45:55 to ensure the formation of PLGA5050. CONCLUSION: The screened out synthesis technique can obtain PLGA5050 with Mw of 52000 and coefficient of distribution between 1.5-1.7 at atmospheric pressure, and its quality is controllable.

OBJECTIVE: To develop an LC-MS/MS method for determination of irinotecanin nanoparticles and its metabolite SN-38 in rats whole blood. METHODS: The drugs were using liquid-liquid extraction method in rats of whole blood, with diazepam as an internal standard. The Shim-pack XR-ODS (2.0 mm×100 mm, 2.2 μm) column was used. The gradient mobile phase consisted of 5 mmol·mL-1 ammonium formates solution (A) and Acetonitrile (B) at the flow rate of 0.3 mL·mL-1, the injection volume was 10 μL and the column temperature was 35°C. The total time of the analysis was 4.2 min. Electrospray ionization sourceand selective ion monitoringwere employed. RESULTS: The linear ranges of irinotecan and SN-38 were 1-2000 and 0.5-100 ng·mL-1, respectively; lower limit of quantification (LLOQ) was 1 and 0.5 ng·mL-1, respectively; the intra-batch RSD were less than 9.43% and 11.39%, respectively, the inter-batch RSD were less than 9.73% and 11.79%, respectively. The extraction recoveries were 73.7%-117.4% and 61.7%-75.5%, respectively. CONCLUSION: The method had less interference and is sensitive, accurate for the determination of irinotecan and its metabolite SN-38 in the whole blood of rats.

OBJECTIVE: To study the pharmacokinetics of intravenous busulfan in Chinese adult patients undergoing allogeneic hematopoietic stem cell transplantation and its correlation with clinical outcome. METHODS: Blood specimens of 34 patients were collected following the first, fifth and seventh dose of an intravenous administration of busulfan at 1.6 mg·kg-1 every 12 hours for 4 days. The concentrations of busulfan in blood plasma were determined by LC-MS. The pharmacokinetic parameters were calculated according to non-compartment model by WinNoLin statistical software. RESULTS: The pharmacokinetics behavior after dose 1 and dose 7 of intravenous busulfan in 34 patients were all fit to a one compartment model. The main pharmacokinetic parameters were as follow: CL (4.1±1.8), (4.6±1.9) mL·min-1·kg-1; Vd (1.3±0.5), (1.2±0.5) L·kg-1; AUC0-12 (1218.5±351.0), (1501.2±444.3)μmol·min·L-1; AUC0-∞ (1694.8±741.7), (1882.2±754.1) μmol·min·L-1; cav(1.8±0.6), (2.2±0.7) μmol·L-1. AUC and cav of dose 7 were higher than dose 1 (P<0.05). The patient's body weight negatively correlated with CL (P<0.05). CONCLUSION: The pharmacokinetics profiles of twice-daily intravenous busulfan are fit to a one compartment model. The pharmacokinetics of busulfan varied in different doses and patients. Therapeutic drug monitoring (TDM) of busulfan will be important to clinical treatment.

OBJECTIVE: To develop an HPLC method for simultaneous determination of multiple-components in Hedyotis diffusa Willd. METHODS: The HPLC analysis was carried out on a C18 column (4.6 mm×250 mm, 5 μm) by gradient elution with acetoni-trile-water[both containing 0.1‰ (V/V) acetic acid] as mobile phase at a flow rate of 0.8 mL·min-1, the column temperature at 35°C, and the detection wavelength was set at 238 nm. External standard method and quantitative analysis of multi-components by single marker (QAMS) method were adopted for simultaneous determination of six components in Hedyotis diffusa Willd, respectively. RESULTS: The linear ranges for asperulosidic acid, quercetin-3-O-[2-O-(6-O-E-feruloyl)-β -D-glucopyranosyl]-β-D-glucopyrano-side, kaempferol-3-O-[2-O-(6-O-E-feruloyl)-β-Z) -gfucopyranosyl]-β-D-galactopyranoside, (E)-6-O-p-coumaroyl scandoside methyl ester, (E)-6-O-feruloyl scandoside methyl ester, (Z)-6-O-p-coumaroyl scandoside methyl ester were 2.34-93.50, 2.61-104.33, 0.67-26.69, 3.42-136.84, 0.65-26.07, and 1.10-44.17 μg·mL-1 (r<0.9993), respectively. The RSD values of precision, reproducibility, and sample stability were not more than 2.2%. The average recoveries of the six components were 99.8%-101.1% with RSDs not more than 1.2%. The P values of external standard method and QAMS by paired t-test were greater than 0.05. CONCLUSION: There is no significant difference in the content analysis results of the two methods, which can both used for simultaneous determination of the four iridoids and two flavonoids in Hedyotis diffusa Willd.

OBJECTIVE: To establish evaluation methods of the quality and quality equivalence of Gentiana rigescens Franch. from different populations. METHODS: The contents of the active ingredients, gentiopicroside, swertiamarin and sweroside in the roots of Gentiana rigescens Franch., were determined by HPLC, and the HPLC fingerprint was established. The quality and quality e-quivalence were evaluated by One-way ANOVA, cluster analysis and principal component analysis (PCA). RESULTS: The overall quality of Gentiana rigescens Franch. from different populations in Dali Yunnan was better. The content of gentiopicroside in the sample from Weishan population was lower than those in the other populations, while it was more than twice the national standard. There was significant difference (P<0.01) in the contents of gentiopicroside, swertiamarin, and sweroside in the roots of Gentiana rigescens Franch. from different populations. The quality equivalence of Gentiana rigescens Franch. from different populations was analyzed, and 11 common peaks in HPLC fingerprint were selected to evaluate the similarities of the crude drugs. The similarities of the characteristic peaks were all above 0.988. The three characteristic peaks of gentiopicroside, swertiamarin and sweroside which were related to the activity of Gentiana rigescens Franch were identified, and the qualities of different populations were basically equivalent. The total contents of gentiopicroside, swertiamarin and sweroside of Gentiana rigescens Franch. from different populations were similar as shown by cluster analysis and PCA of HPLC fingerprint. CONCLUSION: Jianchuan and Heqing polulations are quality germplasm populations according to the contents of effective components and HPLC fingerprint. The evaluation methods of quality and quality equivalence of Gentiana rigescens Franch. from different populations are established, which would provide the theoretical basis for further filtering of quality germplasm resources of Gentiana rigescens Franch. from wild populations.

OBJECTIVE: To develop an HPLC-MS method for qualitative and quantitative analysis of nine antiviral agents illegally adulterated in traditional Chinese medicines. METHODS: The samples were separated on a CAPCELL PAK CR 1:4 column (2.0 mm × 150 mm, 5 μm) by gradient elution with 0.1% formic acid solution(adjusted to pH 3.5 with ammonium hydroxide) as the mobile phase A and acetonitrile as the mobile phase B. The gradient elution program was as follows: 0-12 min (90% A→48% A), 12-15 min (48% A→20% A), 15-19 min (20% A→15% A), 19-20 min (90% A). The flow rate was 0.2 mL·min-1 and the injection volume was 5 μL. After being separated by HPLC, the test solution was analyzed by mass spectrometer operated in positive ion mode and in product mode and SRM mode. RESULTS: The calibration curves of the nine antiviral agents showed good linearity and the correlation coefficients were more than 0.998. The recoveries at 3 spiked levels were in the range of 80.6%-117.7%. The limits of quantification were in the range of 0.1-1 μg·g-1. The fragmentation pattern of the nine antiviral agents was summarized. CONCLUSION: The method is sensitive, specific, accurate and applicable to detect the nine antiviral agents in traditional Chinese medicines.

OBJECTIVE: To establish a method for determining nine residual solvents in cefotetan disodium by headspace gas chromatography. METHODS: The residual solvents including methanol, acetone, acetonitrile, dichloromethane, butanone, ethyl ace-late, tetrahydrofuran in cefotetan disodium were quantitatively determined on a DB-624 column (30 m×0.32 mm, 1.8 μm). Water was solvent media. The residual solvents of anisole and isocaprylic acid in cefotetan disodium were quantitatively determined on a HP-FFAP column (25 m×0.32 mm, 0.5 μm). The 20% dimethylsulfoxide (DMSO) was used as the solvent. RESULTS: Nine residual solvents were completely separated. Good linearity of the solvents were obtained within the determination ranges. There between 0.9988 and 0.9997. The average recoveries of three levels were in the range of 95.71%-103.55%. The RSDs were 0.39%-2.28%. CONCLUSION: The established two methods are accurate and sensitive, and can be used for the determination of residual solvents in cefotetan disodium.

OBJECTIVE: To systematically analyze the efficiency and safety of sorafenib in treating renal cell carcinoma. METHODS: Searched in databases of Pubmed, Medline, Cochrane library as well as domestic VIP, CNKI and Wanfang for literature ibout randomized controlled trials of sorafenib in RCC treatment, the deadline was on May 1, 2013. Evaluated the quality of these literature and made a Meta-analysis. RESULTS: Three RCT studies were included, about 1157 patients. Meta-analysis indicated that the efficiency (OR=1.88, 95% CI=1.48-2.39) and safety (OR=1.68, 95% CI=1.27-2.22) between sorafenib and other treatments, vas significant. CONCLUSION: Based on the meta-analysis, sorafenib has a significant advantage in RCC treatment to compare with other traditional scheme, but its higher incidence rate of adverse events may result to adjust the dose in the clinical application, or even feed to interrupt the treatment.