84.2 and 139.2 --> 98.1 was used for the detection of 4PP and the internal standard (IS), 1-piperidineproprionitrile, respectively.Results: The assay was linear from 14.8 to 591.0 nM with absolute recoveries of 4PP (59.1 nM) and IS (143.7 nM) of 85.7% (n = 10) and 86.7% (n = 10), respectively. The accuracy and imprecision of the method (total) was > or = 96.8% and < or = 8.5% over the concentration range studied, respectively. 4PP was detectable in plasma following the administration of 125, 350, 500 mg/m2 and 600 mg/m2 CPT-11 to patients, with AUC(4PP) correlated with the dose (r2 = 0.66). Plasma concentrations of 4PP declined slowly with a long terminal half-life (33.4 +/- 17.1 h).Conclusions: Overall, the concentrations of 4PP in plasma were in the sub-micromolar range (< 206.9 nM) and substantially lower than those capable of inducing apoptosis of cancer cells. [ABSTRACT FROM AUTHOR]
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| Autor: |
Dodds, Helen M., Clarke, Stephen J., Findlay, Michael, Bishop, James F., Robert, Jacques, Rivory, Laurent P., Dodds, H M, Clarke, S J, Findlay, M, Bishop, J F, Robert, J, Rivory, L P |
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| Zdroj: |
Cancer Chemotherapy & Pharmacology; Jan2000, Vol. 45 Issue 1, p9-14, 6p |
| Abstrakt: |
Purpose: To investigate the clinical relevance of 4-piperidinopiperidine (4PP) in the activity of irinotecan (CPT-11), a high-performance liquid chromatography-turboionspray-tandem mass spectrometry assay for plasma 4PP was developed.Methods: Plasma samples were prepared for analysis following C18 solid-phase extraction. Chromatography was performed on a Waters Nova-Pak Phenyl column. Selected reaction monitoring with the mass transitions m/z 169.2 --> 84.2 and 139.2 --> 98.1 was used for the detection of 4PP and the internal standard (IS), 1-piperidineproprionitrile, respectively.Results: The assay was linear from 14.8 to 591.0 nM with absolute recoveries of 4PP (59.1 nM) and IS (143.7 nM) of 85.7% (n = 10) and 86.7% (n = 10), respectively. The accuracy and imprecision of the method (total) was > or = 96.8% and < or = 8.5% over the concentration range studied, respectively. 4PP was detectable in plasma following the administration of 125, 350, 500 mg/m2 and 600 mg/m2 CPT-11 to patients, with AUC(4PP) correlated with the dose (r2 = 0.66). Plasma concentrations of 4PP declined slowly with a long terminal half-life (33.4 +/- 17.1 h).Conclusions: Overall, the concentrations of 4PP in plasma were in the sub-micromolar range (< 206.9 nM) and substantially lower than those capable of inducing apoptosis of cancer cells. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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