RESUMO
An on-line solid phase extraction-high performance liquid chromatography ( SPE-HPLC ) system was applied in the plasma pharmacokinetic study of highly active anti-cancer compound tyrosine kinase inhibitors (TEB-415) in mouse. The on-line SPE-HPLC method associated with Ultimate3000 system which was applied to the determination of the blood drug level of TEB-415 in mouse plasma. C18 column ( Venusil MP, 150 mm × 4. 6 mm, 5μm) was used as analytical column and the mobile phase consisted of acetonitrile-5 mmol/L monopotassium phosphate buffer ( pH 3 . 5 ) at a flow rate of 1 . 0 mL/min was used as the isocratic elution. An MF Ph-1 column (10 mm×4 mm, 5 μm) was used as on-line SPE column, and water and water-acetonitrile were used as the washing solvent and elution solvent respectively. The detection wavelength was set at 262 nm. The pharmacokinetic parameters were calculated by WinNonlin 5. 2 software. The linear range of the calibration curve was between 100 and 20000 μg/L, and the limit of qualification was 20 μg/L. The extraction recovery was between 90 . 5% and 94 . 6%. The RSD of intra-day and inter-day precision was less than 3. 5%. The accuracy of short-term stability, freeze-thaw stability and long-term stability were between 91. 49% and 101. 96%. After oral medication, the mean peak time (Tmax) of TEB-415 in mice was 5. 29 h, and the mean maximum concentration ( Cmax) was 3403μg/L. The area under the curve ( AUC) of TEB-415 was 24600 μg/L·h. This drug's mean half-life was 3. 84 h, and its mean retention time (MRT) was 6. 56 h. These parameters suggested that TEB-415 had appropriate rate of absorption and elimination with preferable bioavailability.
RESUMO
Objective To explore the effect of tiotropium bromide combined with ambroxol hydrochloride oral liquid on chronic obstructive pulmonary disease (COPD) at remission.Methods According to the digital table, 38 patients with COPD at remission were randomly divided into treatment group and control group .The control group was given with conventional treatment ,and anti-infection and symptomatic treatment when acute attacking ,while the treatment group was treated with inhaled tiotropium bromide and ambroxol Hydrochloride oral liquid base on the con -trol group.Both groups were treated and observed for 6 months.Times of expectoration and acute attack of COPD were observed,and scores of COPD Assessment Test ( CAT) were noted everyday during therapy .Results Compared with the control group ,the total times and means of expectoration in treatment group were much less ,with very significant statistical difference(t=5.19,P<0.05);the cases,times and means of acute attack of COPD were obviously less than those in control group,with very significant statistical difference (t=2.92,P<0.05);the total scores and means of CAT in treatment group were much lower,with significant statistical difference(t=2.65,P<0.05).Conclusion With long-term treatment ,inhaled tiotropium bromide combined with ambroxol hydrochloride oral liquid can effectively decrease the times of expectoration and acute attack in patients with COPD at remission,and improve their qualities of life.