| It is widely believed that cancer is one of the serious diseases to harm mankind' s healthy at present. It' s a important means to control pathogenetic condition , decrease the aversion of cancer cell and prolong patients' life span by using anticancer drugs. But most of chemotherapeutics impact the functions of normal organism cells' structures metabolism, splitting and proliferation seriously at the time they kill cancer cell, so they cause damage to human body. The common adverse reactions in clinic are hepar and renal functional lesion, cordis damage, bone marrow depressions anaemias alopecia and infecting et al. Among these, nausea and vomiting induced by hepar and renal functional lesion brings the greatest anguish to patients, it often causese therapeutics cannot insist. Azasetro Hydrochloride is a potent , high selective, security and hyp-side-effective 5-HT3 receptor anatagonist, it has drastic intercept effect with regard to 5-HT3 receptor, It is effective agents in the prevention and management of nausea and vomiting induced by cancer chemotherapy, so it brings into full play in tumor therapy.Azasetro Hydrochloride, which was co-explored by Yoshitomi Pharm Ind. Ltd. and Japan Tobacco. Inc, first went on the market on 1994 in Japen. Since the research of Azasetro Hydrochloride and its praeparatum was started in china recent years, quality standard of Azasetro Hydrochloride has not been recorded into China pharmacopeia yet. Its chemical identification, determination of general and related substance and assaying were determinated based on its structure property and its quality standard of Azasetro Hydrochloride (protocol) was established. Volumetric precipitation method was applied for the determination of content of Sodium Chloride; RP-HPLC was developed for the assay of content and drug-related Impurities. Azasetro Hydrochloride and its related substance were separated on the Hypersil C18 column ( 250x4.6mm, 10μm ) with phosphate buffer (pH3.0, 30mmol/L)-methanol(63:37) as the mobile phase and detected at 330nm. The calibration curve was linear (r = 0.9999) within the range of 50.0 ~ 400.0μg/ml for Azasetro Hydrochloride, the detection limit was 0.4 μ g ( S/N=3 ) , the analysis precision RSD was less than 1.0 % (n=5), the repeatability precision RSD was 0.47% (n=6), and the average recovery was 100.9%, and the limit of drug-related impurities was 1.0%. Its characters content and related substance were also examedduring 6 months' acceleration under 40℃ and 1 year' s standing under commom temperature based on quality standard already established. This method was simple accurate and suitable for the quality control for Azasetro Hydrochloride.Metabolism principle and pharmacokinetics of Azasetro Hydrochloride in rabbits in vivo were investigated in this study. Liquid-liquid extraction method was chosen to pretreat plasma samples before RP-HPLC analysis. Azasetro Hydrochloride was separated on Hypersil C18 column (250×4.6mm, 10μm) with phosphate buffer (pH3.0, 30mmol/L)-methanol(65:35) as the mobile phase by RP-HPLC and detected at 220nm. The calibration curve was linear (r > 0.9999) within the range of 0.060~50.00 mg/L for Azasetro Hydrochloride. The detection limit was 8ng (S/N>3). The analytical recovery was more than 95%. Intra-day and inter-day precision all less than 5.0% (n=5). The reliability of this method is high enough to perform quantitative analysis of Azasetro Hydrochloride in plasma samples.The pharmacokinetics study of Azasetro Hydrochloride was performed in 8 healthy rabbits after intraperitoneal (i.p.) injection with single dosage by the established analytical method. The experimental data showed that the concentration-time curve of Azasetro Hydrochloride in rabbit plasma could be fitted to two-compartment model, and the main pharmacokinetic parameters were as follows: the area under the plasma concentration-time curve (AUC) was 2.4432±0.7313 ( mg/L ) h, the peak plasma concentration (Cmax) was 1.7395±0.3207mg/L, the peak time (Tmax) was 0.2542 ±0.1231h, the absorption half life (t1/2, ka) was 0.1134±0.0858 h , the distribution half life (t1/2. a) was 0.2509±0.1741 h, the elimination half life (t1/2. β ) was 2.0578±1.8616 h, the clearance (CL) was 2.1728±0.5014 mg/kg/h (mg/L), and the volume of apparent distribution (V/F) was 1.7050±0.4810 (mg/kg) /(mg/L). It was also proved that Azasetro Hydrochloride was absorpted into blood and eliminated quickly. These findings could provide reference for clinical rational administration, moreover offer medical data in vivo for studying Azasetro Hydrochloride' s correlated dosage forms.
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