Analysis of the active lactone form of 9-aminocamptothecin in plasma using solid-phase extraction and high-performance liquid chromatography

Chris H. Takimoto; Raymond W. Klecker; William L. Dahut; Lorrin K. Yee; John M. Strong; Carmen J. Allegra; Jean L. Grem

doi:10.1016/0378-4347(94)00051-4

Analysis of the active lactone form of 9-aminocamptothecin in plasma using solid-phase extraction and high-performance liquid chromatography

Chris H. Takimoto, Raymond W. Klecker, William L. Dahut, Lorrin K. Yee, John M. Strong, Carmen J. Allegra, Jean L. Grem

Research output: Contribution to journal › Article › peer-review

62 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	97-104
Number of pages	8
Journal	Journal of Chromatography B: Biomedical Sciences and Applications
Volume	655
Issue number	1
DOIs	https://doi.org/10.1016/0378-4347(94)00051-4
State	Published - Apr 22 1994
Externally published	Yes

ASJC Scopus subject areas

General Chemistry

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10.1016/0378-4347(94)00051-4

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Takimoto, C. H., Klecker, R. W., Dahut, W. L., Yee, L. K., Strong, J. M., Allegra, C. J., & Grem, J. L. (1994). Analysis of the active lactone form of 9-aminocamptothecin in plasma using solid-phase extraction and high-performance liquid chromatography. Journal of Chromatography B: Biomedical Sciences and Applications, 655(1), 97-104. https://doi.org/10.1016/0378-4347(94)00051-4

Analysis of the active lactone form of 9-aminocamptothecin in plasma using solid-phase extraction and high-performance liquid chromatography. / Takimoto, Chris H.; Klecker, Raymond W.; Dahut, William L. et al.
In: Journal of Chromatography B: Biomedical Sciences and Applications, Vol. 655, No. 1, 22.04.1994, p. 97-104.

Research output: Contribution to journal › Article › peer-review

Takimoto, CH, Klecker, RW, Dahut, WL, Yee, LK, Strong, JM, Allegra, CJ & Grem, JL 1994, 'Analysis of the active lactone form of 9-aminocamptothecin in plasma using solid-phase extraction and high-performance liquid chromatography', Journal of Chromatography B: Biomedical Sciences and Applications, vol. 655, no. 1, pp. 97-104. https://doi.org/10.1016/0378-4347(94)00051-4

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title = "Analysis of the active lactone form of 9-aminocamptothecin in plasma using solid-phase extraction and high-performance liquid chromatography",

abstract = "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.",

author = "Takimoto, {Chris H.} and Klecker, {Raymond W.} and Dahut, {William L.} and Yee, {Lorrin K.} and Strong, {John M.} and Allegra, {Carmen J.} and Grem, {Jean L.}",

note = "Funding Information: °NCl-Navy Medical Oncology Branch, Division of Cancer Treatment, National Cancer Institute, National Naval Medical Center, Bethesda, MD 20889, USA bDivision of Clinical Pharmacology, Office of Research Resources, Center For Drug Evaluation and Research, Food and Drug, administration, 4 Research Court, Rockville, MD 20850, USA",

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doi = "10.1016/0378-4347(94)00051-4",

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T1 - Analysis of the active lactone form of 9-aminocamptothecin in plasma using solid-phase extraction and high-performance liquid chromatography

AU - Takimoto, Chris H.

AU - Klecker, Raymond W.

AU - Dahut, William L.

AU - Yee, Lorrin K.

AU - Strong, John M.

AU - Allegra, Carmen J.

AU - Grem, Jean L.

N1 - Funding Information: °NCl-Navy Medical Oncology Branch, Division of Cancer Treatment, National Cancer Institute, National Naval Medical Center, Bethesda, MD 20889, USA bDivision of Clinical Pharmacology, Office of Research Resources, Center For Drug Evaluation and Research, Food and Drug, administration, 4 Research Court, Rockville, MD 20850, USA

PY - 1994/4/22

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N2 - 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.

AB - 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.

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Analysis of the active lactone form of 9-aminocamptothecin in plasma using solid-phase extraction and high-performance liquid chromatography

Abstract

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