Analysis of the active lactone form of 9-aminocamptothecin in plasma using solid-phase extraction and high-performance liquid chromatography.
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.
Takimoto
C H
CH
NCI-Navy Medical Oncology Branch, Division of Cancer Treatment, National Cancer Institute, National Naval Medical Center, Bethesda, MD 20889.
Klecker
R W
RW
Dahut
W L
WL
Yee
L K
LK
Strong
J M
JM
Allegra
C J
CJ
Grem
J L
JL
D000970:Antineoplastic Agents / Q000097:blood*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006868:Hydrolysis; D007202:Indicators and Reagents; D013050:Spectrometry, Fluorescence
D000970:Antineoplastic Agents; D007202:Indicators and Reagents; C080125:9-aminocamptothecin; D002166:Camptothecin