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匹苯齐莫(双苯并咪唑)的高效液相色谱测定及临床前药理学研究

High-performance liquid chromatographic assay and preclinical pharmacological studies of pibenzimol (bisbenzimidazole).

作者信息

Ames M M, Miller K J, Moertel D M

出版信息

J Chromatogr. 1985 May 31;341(1):89-96. doi: 10.1016/s0378-4347(00)84012-8.

DOI:10.1016/s0378-4347(00)84012-8
PMID:2410440
Abstract

A sensitive and selective high-performance liquid chromatographic assay with ultraviolet or fluorescence detection has been developed for the experimental antitumor agent pibenzimol. Drug is isolated from plasma or other aqueous solutions with reversed-phase C18 disposable extraction columns and chromatography afforded with a deactivated reversed-phase C18 column and phosphate buffer--methanol mobile phase. Plasma standard curves are linear for concentrations for pibenzimol from 0.01 to 5.0 micrograms/ml. Pibenzimol is stable in fresh human plasma and whole blood. Pibenzimol appears to bind to plasma proteins; however, drug adsorption to glass, plastic, membranes, and filters precludes accurate determination of pibenzimol plasma protein binding. Plasma concentrations of pibenzimol fall rapidly following rapid intravenous administration to rabbits, but parent drug is detectable in plasma 24 h after drug administration. The 24-h urinary recovery of pibenzimol is 10-20%.

摘要

已开发出一种灵敏且具选择性的高效液相色谱分析法,采用紫外或荧光检测,用于实验性抗肿瘤药物匹苯齐莫。药物通过反相C18一次性萃取柱从血浆或其他水溶液中分离出来,然后用去活化的反相C18柱和磷酸盐缓冲液 - 甲醇流动相进行色谱分析。匹苯齐莫在血浆中的标准曲线在0.01至5.0微克/毫升的浓度范围内呈线性。匹苯齐莫在新鲜人血浆和全血中稳定。匹苯齐莫似乎与血浆蛋白结合;然而,药物对玻璃、塑料、膜和过滤器的吸附妨碍了对匹苯齐莫血浆蛋白结合的准确测定。对兔子快速静脉给药后,匹苯齐莫的血浆浓度迅速下降,但给药24小时后血浆中仍可检测到母体药物。匹苯齐莫24小时的尿回收率为10 - 20%。

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Phase I-II study of pibenzimol hydrochloride (NSC 322921) in advanced pancreatic carcinoma.盐酸匹苯齐莫(NSC 322921)用于晚期胰腺癌的I-II期研究。
Invest New Drugs. 1991 Feb;9(1):53-7. doi: 10.1007/BF00194545.