ANALYSIS OF THE ACTIVE LACTONE FORM OF 9-AMINOCAMPTOTHECIN IN PLASMA USING SOLID-PHASE EXTRACTION AND HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

被引：61

作者：

TAKIMOTO, CH ^{[1
]}

KLECKER, RW ^{[1
]}

DAHUT, WL ^{[1
]}

YEE, LK ^{[1
]}

STRONG, JM ^{[1
]}

ALLEGRA, CJ ^{[1
]}

GREM, JL ^{[1
]}

机构：

[1] US FDA,CTR DRUG EVALUAT & RES,OFF RES RESOURCES,DIV CLIN PHARMACOL,ROCKVILLE,MD 20850

来源：

JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS | 1994年 / 655卷 / 01期

关键词：

D O I：

10.1016/0378-4347(94)00051-4

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

We have developed a sensitive HPLC assay to quantitate the active lactone form of 9-aminocamptothecin (9AC) in human plasma over the concentration range 10-0.25 nM (0.091 ng/ml). Solid-phase extraction separated 9AC lactone from its less active metabolite, 9AC carboxylate, allowing samples to be stored for up to two months prior to reversed-phase HPLC analysis. An acidic (pH 2.55) isocratic HPLC mobile phase was used to enhance 9AC fluorescence resulting in an over 50-fold increase in assay sensitivity compared to previous methods. This assay was able to measure steady-state 9AC lactone concentrations even at the lowest dose level of 9AC used in our Phase I clinical trial.

引用

页码：97 / 104

页数：8

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