Abstract
E-3810, 6-[[7-[(1-aminocyclopropyl)methoxy]-6-methoxy-4-quinolyl]oxy]-N- methyl-naphthalene-1-carboxamide, is a novel, potent, dual inhibitor of vascular endothelial growth factor and fibroblast growth factor receptors with antiangiogenic properties, now under early clinical evaluation as an anticancer agent. To investigate its clinical pharmacokinetics, a high-performance liquid chromatography-tandem mass spectrometry method was developed and validated to measure the drug in human plasma on the basis of simple protein precipitation with methanol after addition of deuterated E-3810 as internal standard. The method requires a small volume of sample (100 μl) and is rapid and selective, allowing good resolution of peaks in 5 min. It is sensitive, precise, and accurate, with overall precision, expressed as CV%, always ≤7.1%, accuracy in the range 92.7%-104.4%, and high recovery, close to 100%. The limit of detection is 0.01ng/ml, and the lower limit of quantitation is 2.0ng/ml. The assay was validated in the range from the lower limit of quantitation up to 500.0ng/ml. This is the first method developed and validated for analyzing E-3810 in human plasma. The method has been successfully applied to study E-3810 pharmacokinetics in cancer patients with solid tumors who are receiving daily oral doses of the drug during the phase I trial.
| Original language | English |
|---|---|
| Pages (from-to) | 1039-1045 |
| Number of pages | 7 |
| Journal | Journal of Mass Spectrometry |
| Volume | 46 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 2011 |
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Keywords
- E-3810
- FGFR/VEGFR inhibitor
- HPLC-MS/MS
- pharmacokinetics
- phase I study
ASJC Scopus subject areas
- Spectroscopy
Cite this
Development and validation of a high-performance liquid chromatography-tandem mass spectrometry method for the determination of the novel inhibitor of angiogenesis E-3810 in human plasma and its application in a clinical pharmacokinetic study. / Sala, Federica; Bagnati, Renzo; Livi, Valeria; Cereda, Roberta; D'Incalci, Maurizio; Zucchetti, Massimo.
In: Journal of Mass Spectrometry, Vol. 46, No. 10, 10.2011, p. 1039-1045.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Development and validation of a high-performance liquid chromatography-tandem mass spectrometry method for the determination of the novel inhibitor of angiogenesis E-3810 in human plasma and its application in a clinical pharmacokinetic study
AU - Sala, Federica
AU - Bagnati, Renzo
AU - Livi, Valeria
AU - Cereda, Roberta
AU - D'Incalci, Maurizio
AU - Zucchetti, Massimo
PY - 2011/10
Y1 - 2011/10
N2 - E-3810, 6-[[7-[(1-aminocyclopropyl)methoxy]-6-methoxy-4-quinolyl]oxy]-N- methyl-naphthalene-1-carboxamide, is a novel, potent, dual inhibitor of vascular endothelial growth factor and fibroblast growth factor receptors with antiangiogenic properties, now under early clinical evaluation as an anticancer agent. To investigate its clinical pharmacokinetics, a high-performance liquid chromatography-tandem mass spectrometry method was developed and validated to measure the drug in human plasma on the basis of simple protein precipitation with methanol after addition of deuterated E-3810 as internal standard. The method requires a small volume of sample (100 μl) and is rapid and selective, allowing good resolution of peaks in 5 min. It is sensitive, precise, and accurate, with overall precision, expressed as CV%, always ≤7.1%, accuracy in the range 92.7%-104.4%, and high recovery, close to 100%. The limit of detection is 0.01ng/ml, and the lower limit of quantitation is 2.0ng/ml. The assay was validated in the range from the lower limit of quantitation up to 500.0ng/ml. This is the first method developed and validated for analyzing E-3810 in human plasma. The method has been successfully applied to study E-3810 pharmacokinetics in cancer patients with solid tumors who are receiving daily oral doses of the drug during the phase I trial.
AB - E-3810, 6-[[7-[(1-aminocyclopropyl)methoxy]-6-methoxy-4-quinolyl]oxy]-N- methyl-naphthalene-1-carboxamide, is a novel, potent, dual inhibitor of vascular endothelial growth factor and fibroblast growth factor receptors with antiangiogenic properties, now under early clinical evaluation as an anticancer agent. To investigate its clinical pharmacokinetics, a high-performance liquid chromatography-tandem mass spectrometry method was developed and validated to measure the drug in human plasma on the basis of simple protein precipitation with methanol after addition of deuterated E-3810 as internal standard. The method requires a small volume of sample (100 μl) and is rapid and selective, allowing good resolution of peaks in 5 min. It is sensitive, precise, and accurate, with overall precision, expressed as CV%, always ≤7.1%, accuracy in the range 92.7%-104.4%, and high recovery, close to 100%. The limit of detection is 0.01ng/ml, and the lower limit of quantitation is 2.0ng/ml. The assay was validated in the range from the lower limit of quantitation up to 500.0ng/ml. This is the first method developed and validated for analyzing E-3810 in human plasma. The method has been successfully applied to study E-3810 pharmacokinetics in cancer patients with solid tumors who are receiving daily oral doses of the drug during the phase I trial.
KW - E-3810
KW - FGFR/VEGFR inhibitor
KW - HPLC-MS/MS
KW - pharmacokinetics
KW - phase I study
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U2 - 10.1002/jms.1985
DO - 10.1002/jms.1985
M3 - Article
VL - 46
SP - 1039
EP - 1045
JO - Biomedical Mass Spectrometry
JF - Biomedical Mass Spectrometry
SN - 1076-5174
IS - 10
ER -