ABSTRACT
Objective:To study the effects and mechanisms of acetyl-11-keto-β-boswellic acid ( AKBA) in myocardial ischemic model induced by isoproterenol hydrochloride ( ISO) in rats. Methods:The SD rats were randomly divided into the sham group, model group, AKBA low dose group and AKBA high dose group. Myocardial injury model was induced by subcutaneous injection of ISO (100 mg·kg-1 ) . The change of ST segment in ECG was observed. Creatine kinase ( CK-MB) , cardiac troponin I ( cTnI) , lactate dehydro-genase( LDH) , malondialdehyde( MDA) and superoxide dismutase( SOD) in the blood were detected by ELISA. The change of histo-logical tissue was determined by HE staining, and cell apoptosis was analyzed by TUNEL assay. Results: Serum CK-MB, cTnI and LDH were decreased significantly in AKBA high dose group when compared with those in the model group. Compared with that in the model group, MDA content was lowered and the SOD activity was increased in AKBA high dose group. Furthermore, AKBA high dose group improved the pathologic changes of myocardium. TUNEL assay revealed significant reduction of cardiomyocytes apoptosis in the hearts of the ischemic rats in AKBA high dose group. Conclusion:AKBA has excellent cardioprotective effect on myocardial ischemic induced by ISO and protection of myocardial cells from injury.
ABSTRACT
A convenient and rapid HPLC method was developed for the determination of clinofibrate in human plasma using simple protein precipitation with the mixture of acetonitrile and 1M hydrochloric acid (95:5, v/v) followed by separation using an Inspire C(18) column with isocratic elution. The detection wavelength was 232nm and the flow rate was 1.0ml/min. The mobile phase consisted of acetonitrile and water containing 0.4% ortho-phosphoric acid (73:27, v/v). Linear calibration curve was obtained over the concentrations ranging from 0.5µg/ml to 32µg/ml (r(2)=0.999) with LLOQ of 0.5µg/ml. The RSD in both the intra-run and inter-run precision study was less than 5.4% and the extraction recoveries were above 90.7%. The HPLC method is reproducible and suitable for the quantification of clinofibrate in plasma. This method was successfully applied to the pharmacokinetic studies of clinofibrate in healthy volunteers. The elimination half-lives (t(1/2)) were (20.47±3.44), (18.19±2.62) and (21.51±4.78)h after single oral administration of 200, 400 and 600mg clinofibrate, respectively. The results of WinNonlin software showed that the area under the plasma concentration versus time curve from time 0 to 72h (AUC(0-72)) and peak plasma concentration (C(max)) were linearly related to dose (P>0.05).
Subject(s)
Chromatography, High Pressure Liquid/methods , Hypolipidemic Agents/pharmacokinetics , Phenoxyacetates/pharmacokinetics , Administration, Oral , Adult , Area Under Curve , Calibration , Dose-Response Relationship, Drug , Female , Half-Life , Humans , Male , Reproducibility of Results , Software , Time FactorsABSTRACT
A high-performance liquid chromatographic method was developed for the determination of a new derivative of docetaxel, felotaxel, in rat plasma and human plasma and urine. The separation of felotaxel was performed on a Dikma C18 column with 0.2% formic acid and acetonitrile (50:50) as the mobile phase. The flow rate was 0.8 mL/min and the column effluent was monitored by an ultraviolet detector set at 275 nm. The method was validated and found to be linear in the range of 5-1,000 ng/mL. The lower limit of quantification was 5 ng/mL based on 100 µL of plasma. The variations for intra-day and inter-day precision were less than 6.9%, and the accuracy values were between 87.3 and 107.4%. The extraction recoveries were more than 80.5%. These data confirm that the developed method has satisfactory sensitivity, accuracy and precision for the quantification of felotaxel in rat plasma and in human plasma and urine. The method was successfully applied to a pharmacokinetics study of felotaxel after intravenous doses of 5 mg/kg in rats.
