Determination of risperidone in human plasma by HPLC-MS/MS and its application to a pharmacokinetic study in Chinese volunteers / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

This study presents a rapid, specific and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay for determination of risperidone (RIS) in human serum using paroxetine as an internal standard (IS). An Alltima-C18 column (2.1 mmx100 mm, 3 microm) and a mobile phase consisting of 0.1% formic acid-acetonitrile (40:60, v/v) were used for separation. The analysis was performed by selected reaction monitoring (SRM) method, and the peak area of the m/z 411.3-->191.1 transition for RIS was measured versus that of the m/z 330.1-->192.1 transition for IS to generate the standard curves. The assay linearity of RIS was confirmed over the range 0.25 approximately 50.00 ng/ml and the limit of quantitation was 0.05 ng/ml. The linear range corresponds well with the serum concentrations of the analytes obtained in clinical pharmacokinetic studies. Intraday and interday relative standard deviations were 1.85% approximately 9.09% and 1.56% approximately 4.38%, respectively. The recovery of RIS from serum was in the range of 70.20% approximately 84.50%. The method was successfully applied to investigate the bioequivalence between two kinds of tablets (test versus reference products) in 18 healthy male Chinese volunteers. The result suggests that two formulations are bioequivalent.

Peak concentration of gemcitabine at fixed-dose-rate and its hematological toxicity profile / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the relationship between peak concentration (Cmax) of gemcitabine at fixed-dose-rate and its hematological toxicity profile in patients with advanced non-small-cell lung cancer (NSCLC).</p><p><b>METHODS</b>Twenty-one patients received gemcitabine at a fixed dose rate (1200 mg/m2 over 120 min) with carboplatin. Plasma concentrations of gemcitabine were measured by ion-pair reversed-phase high-performance liquid chromatography.</p><p><b>RESULTS</b>The mean value of Cmax in 21 eligible patients was(4.95+/-2.42) microg *ml(-1). The main hematological toxicity was grade III-IV thrombocytopenia and neutropenia. The mean percentages of reduction of WBC, NEC, PLTC and Hb of 21 patients were (38.3+/-38.1)%, (31.3+/-73.6)%, (31.8+/-53.5)% and (12.0+/-12.2)%, respectively. The C(max)of gemcitabine and the percentage of reduction in WBC showed a significant correlation (r2=0.4575, P<0.05). A significant correlation (r2=0.5671, P<0.05) was also observed between the percentage of reduction of PLTC and Cmaxof gemcitabine.</p><p><b>CONCLUSION</b>The results of relationship between Cmax and toxicity profile suggest that gemcitabine administration should be individualized in order to decrease the occurrence of ADR.</p>

Comparison of pharmacokinetics, efficacy and toxicity profile of gemcitabine using two different administration regimens in Chinese patients with non-small-cell lung cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>OBJECTIVE</b>To conduct a randomized comparative trial of pharmacokinetics, efficacy and toxicity profile treatment with 1200 mg/m(2) gemcitabine using standard 30-min infusion or fixed dose rate (FDR) infusion [10 mg/(m(2) x min)] on days 1 and 8 plus carboplatin AUC (area under curve) 5 on day 1 in Chinese non-small-cell cancer patients. Twelve patients were enrolled in this study.</p><p><b>METHODS</b>Plasma gemcitabine concentrations were measured by ion-pair reversed phase high performance liquid chromatography. Antitumoral activity and toxicity of gemcitabine was assessed according to World Health Organization criteria.</p><p><b>RESULTS</b>The obtained mean parameters, such as T(1/2) (elimination half time), AUC, and CL (clearance), were consistent with those reported in literature. Qualified response rate in our study was 33.3% for standard arm and 50% for FDR arm. Additional 50% and 33.3% patients contracted stable disease (SD) in standard arm and FDR arm, respectively. The predominant toxicity was hematologic, and patients in the standard infusion arm experienced consistently more hematologic toxicity.</p><p><b>CONCLUSION</b>Pharmacokinetic and clinical data in this trial support the continued evaluation of the FDR infusion strategy with gemcitabine.</p>

Effects of different dialysates on apoptosis and expression of PKC? of U937 cell line / 上海第二医科大学学报

Objective To investigate the effects of different dialysates on expression of protein kinase C-? (PKC?) and apoptosis of U937 cell line. Methods Different dialysates were added into culture fluid with U937 cell line at exponential phase of growth, and groups were divided: fluid A+fluid B group (dialysate A+dialysate B), fluid A+fluid B+rottlerin (PKC? specific inhibitor)group, fluid A+powder B group (dialysate A+powder B) and fluid A+powder B + rottlerin group. Besides, blank control group and normal control group were established. Cells were harvested 24 h and 48 h after treatment, morphological changes were observed by Hoechst33258 fluorescence staining, cell apoptosis was measured by Annexin-V-FITC/PI double staining, and expression of PKC? mRNA and protein was detected by RT-PCR and Western blotting, respectively. Results Cell apoptosis significantly increased in fluid A+powder B group, with typical morphology of apoptosis. After treatment for 24 h and 48 h, cell apoptosis rates in fluid A+powder B group were significantly higher than those at corresponding time points in blank control group, normal control group and fluid A+powder B+rottlerin group (P0.05). Conclusion Fluid A+powder B can significantly increase apoptosis of U937 cell line, the mechanism of which may be associated with the up-regulation of expression of PKC?. Compared with fluid A+powder B, fluid A+fluid B is superior in reducing apoptosis of peripheral blood monouclear cells.

Mitogen-activated protein kinase pathway in antitumor effect of toremifene / 上海第二医科大学学报

Objective To study the antitumor effect of toremifene on MCF7 cell lines,and investigate the role of mitogen-activated protein kinase pathway. Methods Inhibitory effect of toremifene alone or combined with MEK inhibitor PD98059 on MCF7 cells was measured by SRB test,and that on phosphorylated ERK was detected by Western blotting.Results Toremifene exhibited a concentration-dependent inhibitory effect on the activity of MCF7 cells.Phosphorylated ERK was significantly inhibited by 5,10 and 20 mmol/L toremifene.Combined with PD98059,toremifene had a significantly enhanced cytotoxity effect,which exceeded that of application alone. Conclusion Mitogen-activated protein kinase pathway may play an important role in the antitumor effect of toremifene which is independent of estrogens.Combined with PD98059,the antitumor effect of toremifene can be reinforced,indicating a synergistic effect of these two drugs.

HPLC determination of metformin hydrochloride-related substances / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To develop a HPLC assay for the determination of metformin hydrochloride-related substances.</p><p><b>METHODS</b>The separation was performed on SHIMADZU VP-ODS (250 4.6 mm, 5 microm) column. The mobile phase of dicyandiamide was composed of methyl alcohol-1 mmol x L(-1) sodium dodecylsulfate in 10 mmol x L(-1) phosphate salt solution (60:40) (pH=5.5). The mobile phase of other related substances was composed of methyl alcohol-1 mmol x L(-1) sodium dodecysulfate in 10 mmol x L(-1) phosphate salt solution (55:45)(pH=5.5). The detection wavelength was 232 nm, and the running speed was 0.8 ml min(-1) at room temperature.</p><p><b>RESULT</b>Good resolution of dicyandiamide and main peak was obtained. The test results were reproducible.</p><p><b>CONCLUSION</b>The method is simple, rapid and suitable for the determination of dicyandiamide and other metformin hydrochloride-related substances.</p>

Study on determination of desloratadine in human serum and its pharmacokinetics by HPLC/MS / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To study the determination of desloratadine in human serum and its pharmacokinetics in healthy volunteers.</p><p><b>METHODS</b>A single oral dose of 10 mg desloratadine was given to 18 healthy volunteers. The serum concentrations of desloratadine were determined by HPLC-MS assay. The pharmacokinetics parameters of desloratadine tablets were calculated with program 3P97.</p><p><b>RESULT</b>The main pharmacokinetics parameters of desloratadine tablets were as followsút(max)(1.611 +/-0.366)h, C(max) (4.455+/-1.990)microg x L(-1), AUC(0-t) (58.50+/-21.34)microg x L(-1) x h(-1), AUC(0-infinity) (60.59+/-22.32)microg x L(-1) x h(-1), t(1/2(ke)) (20.303+/-5.833)h, Ke (0.0372+/-0.0116)h(-1) and CL(0.1838+/-0.0563)L x h(-1).</p><p><b>CONCLUSION</b>Desloratadine tablet is absorbed quicker in the 18 healthy volunteers than the reports and its peak blood concentration reached at 1.5 h after oral administration with t(1/2) 20 h.</p>

Pharmacokinetics of gemcitabine in Chinese patients with non-small-cell lung cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

To determine the pharmacokinetics of gemcitabine (2',2'-difluorodeoxycytidine) in Chinese non-small-cell lung cancer (NSCLC) patients. Six study subjects were administered gemcitabine at a fixed dose rate of 10 mg/m(2) per min (1200 mg/m(2), two hours infusion), and carboplatin and plasma gemcitabine concentrations were measured by ion-pair reversed-phase high-performance liquid chromatography (HPLC). 3P97 Pharmaceutical Kinetics Software was used for the calculation of pharmacokinetic parameters. The obtained mean parameters, elimination half life (t(1/2)) (10.67+/-3.38 min), area under the curve (AUC) (7.55+/-1.53 (microg x h)/ml), and clearance (CL) (3940.05+/-672.08 ml/min), were consistent with those reported in literature. The hematologic toxicology result showed that the regimen was effective on and tolerated by the patients.