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[肝靶向抗疟药新糖白蛋白-伯氨喹共轭物(NGA-PQ)与磷酸伯氨喹在小鼠体内的药代动力学研究]

[Study of pharmacokinetics of liver targeting antimalarial agent neoglycoalbumin-primaquine conjugate (NGA-PQ) and primaquine phosphate in mouse].

作者信息

Li T L, Pang Q J, He Y L, Wang P

机构信息

College of Pharmacy, West China University of Medical Sciences, Chengdu.

出版信息

Yao Xue Xue Bao. 1995;30(10):721-5.

PMID:8701725
Abstract

A normal phase high-performance liquid chromatography process was used to separate and detect primaquine in blood and liver after a single intravenous dose of the hepatic targeting agent neoglycoalbumine-primaquine conjugate (NGA-PQ) and primaquine phosphate (PQP) in mice. 6-Methoxy-8-(4-amino-butyrylamino) quinoline synthesized and identified by us was used as an internal standard to be added to biologic samples obtained from mice at different times after given NGA-PQ or PQP. The mixture was extracted with ether after alkalinization in the PQP group. In the NGA-PQ group, the biological samples must be hydrolized by heating under nitrogen and acid condition in a domestic pressure cooker before extraction. The extracts were evaporated to dryness under nitrogen, then dissolved in the mobile phase (chloroform-methanol-amonium hydroxide = 86.8: 12.5: 0.7). The results showed that the hepatic PQ collecting ratio and the retention time of PQ in liver in the NGA-PQ group were higher and longer than those in the PQP group. The results also point out that NGA-PQ has liver targeting property.

摘要

采用正相高效液相色谱法,在小鼠单次静脉注射肝靶向制剂新糖白蛋白-伯氨喹缀合物(NGA-PQ)和磷酸伯氨喹(PQP)后,对其血液和肝脏中的伯氨喹进行分离和检测。我们合成并鉴定的6-甲氧基-8-(4-氨基丁酰氨基)喹啉用作内标,添加到给予NGA-PQ或PQP后不同时间从小鼠获取的生物样品中。PQP组在碱化后用乙醚萃取混合物。在NGA-PQ组中,生物样品在氮气和酸性条件下于家用压力锅中加热水解后再进行萃取。提取物在氮气下蒸发至干,然后溶解于流动相(氯仿-甲醇-氢氧化铵=86.8:12.5:0.7)中。结果表明,NGA-PQ组肝脏中PQ的摄取率和PQ在肝脏中的保留时间均高于PQP组且更长。结果还指出,NGA-PQ具有肝脏靶向特性。

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