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为了评价盐酸多柔比星脂质体受试制剂(S)和进口同规格参比制剂(R)的一致性,对比研究了2种制剂单次静脉注射后,在SD大鼠和荷人卵巢癌A-2780肿瘤裸鼠的血清和不同组织内的药物浓度。建立了HPLC-FLD法,用于测定SD大鼠血清、荷瘤裸鼠血清和肿瘤中多柔比星(1)总含量(即游离1和PEG化脂质体中1的含量总和)和PEG化脂质体中1含量,以及大鼠不同组织中1的总含量。结果显示,两种制剂以5 mg/kg的剂量,尾静脉注射给予SD大鼠,给药后1 h、24 h和72 h,分别对9个组织脏器中的1总含量进行双单侧检验分析,在P=0.05水平上2种制剂的差异不显著;2种制剂以10 mg/kg的剂量,尾静脉注射给予荷瘤裸鼠,给药后1 h、24 h和72 h分别对瘤内1总含量和PEG化脂质体中1含量进行双单侧检验分析,在P=0.05水平上2种制剂的差异也不显著。由此推断,受试制剂与参比制剂在动物体内的分布无统计学差异。
In order to evaluate the consistency of the tested formulations of doxorubicin hydrochloride (S) and the imported reference formulation (R), the two formulations were compared after a single intravenous injection in SD rats and human ovarian Cancer A-2780 tumor nude mice serum and drug concentrations in different tissues. The HPLC-FLD method was established for the determination of the total content of doxorubicin (1) (ie, the sum of the contents of 1 in free 1 and PEGylated liposomes) and the concentration of PEG in tumor-bearing, tumor-bearing nude mice and tumor 1 in liposomes, and 1 in different tissues of rats. The results showed that the two formulations were given to SD rats via tail vein injection at the dose of 5 mg / kg and at 1, 24 and 72 h after administration, the total contents of 1 in 9 tissues were double unilateral Test and analysis showed that there was no significant difference between the two preparations at the level of P = 0.05. Two kinds of preparations were injected into tail vein at the dose of 10 mg / kg for 1 h, 24 h and 72 h Tumor in 1 total content and PEGylated liposomes 1 content double unilateral test analysis, at the P = 0.05 level, the difference between the two formulations is not significant. It was concluded that there was no significant difference in the distribution of test and reference preparations in animals.