ABSTRACT
OBJECTIVE:To develop a method for the determination of valsartan concentration in human plasma and urine. METHODS:Plasma sample were acidified and extracted with diethyl ether for analysis,and urine sample was diluted directly for analysis. The samples were all determined by LC-MS/MS,and the separation was performed on a Aglient ZORBAX SB-C18 column with mobile phase consisted of acetonitrile and 0.1% formic acid (gradient elution) at flow rate of 0.2 ml/min. Ion transition was determined ESI ion source under multiple ion reaction monitoring with quantitative pair m/z 436.4→253.2 and qualitative ion pair m/z 436.4→291.3 for valsartan,and quantitative pair m/z 423.4→207.1 and m/z 423.4→180.2 for internal standard losartan. RE-SULTS:The linear range of valsartan were 4-5 000 ng/ml in plasma and 20-50 000 ng/ml in urine;the limit of quantification were 4 ng/ml and 20 ng/ml;plasma extraction recovery of valsartan were 61.21%-70.30%. The variation coefficient of internal standard normalized matrix effect were 3.20% and 11.21%. The within-day and between-day RSDs were no more than 8.34%. CONCLU-SIONS:The method is proved to be rapid and sensitive,and suitable for the determination of valsartan in human plasma and urine and pharmacokinetics study.
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Objective To investigate the action mode of borneol on activity of epidermal skin;To investigate action mode of borneol as penetration enhancer. Methods The well-established and standard penetration enhancer Azone was employed as a positive control in this study. The cytotoxicities of borneol and Azone on HaCaT cells were detected by CCK-8 assay, and their half 50% inhibitory concentrations (IC50) were calculated. The fluorescence recovery after photo bleaching was employed to investigate the effect of borneol and Azone on membrane fluidity, and the flow cytometer was used to monitor the changes of membrane potential of HaCaT cell after treated with these penetration enhancers. Results The IC50 values of borneol and Azone were 2.826 , 0.172 mmol/L, respectively. Borneol could significantly improve the membrane fluidity in a concentration-dependent manner, and effectively decrease the membrane potential of HaCaT cell, which exhibited the performances similar to those of Azone. Conclusion The penetration enhancement mechanism of borneol was associated with the concentrations of Ca2+ in keratinocytes, which changes the membrane fluidity and membrane potential of HaCaT cell.
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Objective To investigate the pharmacokinetics of cephapirin sodium in healthy volunteers.Methods Twelve healthy volunteers were enrolled and ad ministered with single doses of 0.5,1.0,4.0 g or multiple doses of 1.0 g cephapirin sodium injection by intravenous drip infusion.The concentrations of cephapirin in human plasma and urine were determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated with WinNonLin 6.3 software. Results The main pharmacokinetic parameters of cephapirin after single dose of 0.5,1.0,4. 0 g and 1.0 g multiple dose cephapirin sodium injection were as follows:Cmaxwere (34.86 ±6.93),(74.77 ±24.23),(319.0 ±44.5),(89.26 ±28.04)μg/mL,AUC0-twere (12.86 ±3.46),(28.31 ±7.46),(163.21 ±34.57),(27.30 ±7.22)μg/(mL·h),t1/2were (0.55 ±0.21),(0.72 ±0.22),(0.71 ±0.27), (0.72 ±0.25),accumulative urine excretion rate of 8 h(1 g)was (44.9 ±12.66)%.Conclusion The process of cephapirin in the dosage range of 0.5 ~4.0 g show linear dynamic feature.There is no accumulation after multiple dosing.Cephapirin sodium was much eli minated from urine in parent drug.
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OBJECTIVE:To study the effects of Shuanghuanglian on pharmacokinetics of theophylline in healthy sub?jects.METHODS:The serum concentration of theophylline was determined by HPLC and analyzed by3p97pharmacokinetic program.RESULTS:The main pharmacokinetic parameters of single theophylline and that in combined use with Shuanghuan?glian were as follows:T max were(1.66?0.56)and(1.59?0.78)h,C max were(6.23?1.31)and(6.10?0.94)?g/ml,T 1/2 were(5.76?1.11)and(6.09?1.63)h,CL were(47.72?5.12)and(50.98?10.85)ml/(kg?h),Vd were(369.18?40.15)and(430.37?48.33)ml/kg,AUC 0～∞ were(84.56?14.43)and(89.27?26.35)?g/(h?ml),respectively.CONCLUSION:The Vd of theophylline were increased(P