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OBJECTIVE：To develop a metho d for determining the plasma concentration of sulfasalazine （SSZ）metabolite sulfapyridine（SP）in rats ，and to investigate the effects of esomeprazole （ESOM）on the pharmacokinetic behavior of SSZ in rats. METHODS：Male SD rats were randomly divided into SSZ group and SSZ+ESOM group ，with 6 rats in each group. SSZ+ESOM group were given Esomeprazole enteric-coated tablets [ 90 mg/（kg·d）] intragastrically for 14 days. On the 15th day ，the rats in 2 groups were given Sulfasalazine enteric coated tablets （90 mg/kg）intragastrically，and blood sample was collected from the inner canthus at 0.5，1，1.5，2，3，4，6，8，10，12，24，36，48，72 h after administration. After protein precipitation with methanol ， using diazepam as internal standard ，Agilent XDR-C 18 column was adopted with methanol- 0.1％ formic acid solution （gradient elution）as mobile phase. The concentration of SSZ metabolite SP in plasma was determined by LC-MS/MS. The pharmacokinetic parameters were calculated by using DAS 3.0.1 software and compared between 2 groups. RESULTS ：The linear range of SP were 2-1 000 ng/mL. The methodology met the requirements of Chinese Pharmacopeia . There was no statistical significance in pharmacokinetic parameters of SP between 2 groups，such as AUC 0－t，tmax，t1/2z，cmax，MRT0－t（P＞0.05）. CONCLUSIONS ：The established method is simple ，rapid and sensitive ；it can be used for the concentration determination of SSZ metabolite SP in plasma. ESOM has no significant effect on the pharmacokinetic behavior of SSZ in rats.
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Objective To develop a HPLC-fluorescence method to determine levofloxacin concentration in plasma for studying bioequivalence of levofloxacin hydrochloride tablet in Chinese healthy volunteers .Methods A single-dose of 0 .2 g test or reference preparation was given to 24 healthy volunteers in a randomized crossover study .The concentrations of levofloxacin at different time points were determined by HPLC with fluorescence detection .The pharmacokinetic parameters were calculated using DAS 2 .0 software program .Results The main pharmacokinetic parameters of the test and reference preparation ,t 1/2 、tmax 、ρmax 、AUC0-36 and AUC0-inf ,were respectively (6 .71 ± 0 .95) h and (6 .60 ± 1 .00) h ,(0 .85 ± 0 .30) h and (0 .79 ± 0 .28) h , (2 815 .48 ± 513 .04 ) ng/ml and (3 185 .59 ± 674 .29 ) ng/ml ,(17 157 .61 ± 1 949 .07 ) ng · h/ml and (17 425 .06 ± 2 447 .80) ng · h/ml ,(18 324 .52 ± 2 019 .41) ng · h/ml and (18 540 .41 ± 2 523 .08) ng · h/ml .The statistical analysis showed that the main pharmacokinetic parameters between test and reference preparations were no significant differences .The 90% confidence interval of test and reference preparations AUC 0-36 、AUC0-inf and ρmax were 95 .2% ~102 .5% 、96 .1% ~102 .2%and 82 .8% ~94.9% .Conclusion The test and reference preparations were bioequivalent .
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The paper reported an investigation of the pharmacokinetics of SN-38 (7-ethyl-10-hydroxy-camptothecin) in rats and the tissue distribution in mice after injection of irinotecan hydrochloride nanoparticles (CPT-11) via tail veins. An LC-MS/MS method was established to determine the concentrations of SN-38 in whole blood of rats and in different tissues of mice. The pharmacokinetics and tissue distribution of SN-38 were compared after the intravenous injection of CPT-11 NPs and CPT-11 solution. Compared with irinotecan solution, the elimination half-life of SN-38 was prolonged from 2.17 h to 2.67 h after the intravenous injection of CPT-11 NPs, but its AUC had little change. After the injection of CPT-11 NPs in mice, over time, the concentrations of CPT-11-metabolized SN-38 in CPT-11 NPs were significantly higher in the whole blood, colon and lungs than those in CPT-11 solution, followed by in the spleen and liver, but those in the heart and brain had no change. However, the amount of SN-38 in the kidneys was reduced with time. CPT-11 NPs could prolong SN-38's (one of its metabolites) blood circulation time in rats and significantly increased the concentration of CPT-11-metabolized SN-38 in the whole blood, colon and lungs of mice. CPT-11 NPs made SN-38 efficiently target-bind to the colon and lungs of mice.
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To investigate the pharmacokinetics of irinotecan hydrochloride (CPT-11) in rats and the tissue distribution of CPT-11 in mice after injection of irinotecan hydrochloride nanoparticles (CPT-11 NPs) via tail veins, separately, a LC-MS/MS method was established to determine the concentration of CPT-11 in whole blood of rats and in different tissues of mice. The pharmacokinetics and tissue distribution of CPT-11 were compared after the intravenous injection of CPT-11 NPs and CPT-11 solution. Compared with CPT-11 solution, the elimination half-life of CPT-11 was prolonged from 2.28 h to 3.95 h after the intravenous injection of CPT-11 NPs, and its AUC was 1.47 times than that of CPT-11 solution. After the injection of CPT-11 NPs in mice, the concentrations of CPT-11 loaded in CPT-11 NPs were significantly higher in the whole blood, colon and lungs than those in CPT-11 solution, but lower in the spleen, liver, kidney and heart, but the least in brain. CPT-11 NPs could improve CPT-11 's AUC, and help CPT-11 to reach long circulation activity.
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The object of this study is to investigate the pharmacokinetic interaction of pioglitazone hydrochloride and atorvastatin calcium in healthy adult Beagle dogs following single and multiple oral dose administration. A randomized, cross-over study was conducted with nine healthy adult Beagle dogs assigned to three groups. Each group was arranged to take atorvastatin calcium (A), pioglitazone hydrochloride (B), atorvastatin calcium and pioglitazone hydrochloride (C) orally in the first period, to take B, C, A in the second period, and to take C, A, B in the third period for 6 days respectively. The blood samples were collected at the first and the sixth day after the administration, plasma drug concentrations were determined by LC-MS/MS, a one-week wash-out period was needed between each period. The pharmacokinetic parameters of drug combination group and the drug alone group were calculated by statistical moment method, calculation of C(max) and AUC(0-t) was done by using 90% confidence interval method of the bioequivalence and bioavailability degree module DAS 3.2.1 software statistics. Compared with the separate administration, the main pharmacokinetic parameters (C(max) and AUC(0-t)) of joint use of pioglitazone hydrochloride and atorvastatin calcium within 90% confidence intervals for bioequivalence statistics were unqualified, the mean t(max) with standard deviation used paired Wilcoxon test resulted P > 0.05. There was no significant difference within t1/2, CL(int), MRT, V/F. Pioglitazone hydrochloride and atorvastatin calcium had pharmacokinetic interaction in healthy adult Beagle dogs.
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OBJECTIVE:To establish a rapid and sensitive HPLC method for simultaneous determination of plasma concentrations of 6 antidepressants.METHODS:With diprozin as internal standard,the alkalized samples were extracted by liquid-liquid extraction and separated on a Phenomenex-C18 column using acetonitrile-0.05 mol?L-1 sodium dihydrogen phosphate(pH was adjusted to 2.5 by phosphoric acid) as mobile phase at a flow rate of 1.2 mL?min-1 by a gradient elution.The column temperature was set at 40℃.Venlafaxine was detected by fluorescence detection at an Ex wavelength of 276 nm and Em wavelength of 598 nm;doxepin,paroxetine,sertraline,fluoxetine and amitriptyline were detected at an UV detection wavelength of 200 nm.RESULTS:The linear ranges of venlafaxine,doxepin,paroxetine,sertraline,fluoxetine and amitriptyline were 5～1 000 ?g?L-1,40 ～200 ?g?L-1,20～800 ?g?L-1,40～1 000 ?g?L-1 and 10～400 ?g?L-1,respectively,with correlation coefficients ≥0.990 for all.Both the intra-day RSD and inter-day RSD were less than 15%;the extraction recovery rates were greater than 60% and methodological recovery were greater than 90% for all the samples.CONCLUSION:The method is simple,economical,rapid,accurate and sensitive,and it is applicable for the clinical monitoring of plasma drug concentrations as well as the analysis and pharmacokinetic study of toxic drugs.