期刊
PHARMACEUTICALS
卷 15, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/ph15050614
关键词
CDK4/6 inhibitors; breast cancer; palbociclib; ribociclib; abemaciclib; anastrozole; letrozole; fulvestrant; therapeutic drug monitoring; LC-MS
资金
- Croatian Science Foundation [HRZZ-UIP2019-04-8461]
A novel bioanalytical LC-ESI-MS/MS method was developed for the quantitation of six breast cancer chemotherapeutic drugs in human plasma. The method was validated and successfully applied to patient samples.
Palbociclib, ribociclib and abemaciclib were recently approved as chemotherapeutic agents and are currently in the post-marketing surveillance phase. They are used in combination with aromatase inhibitors anastrozole and letrozole or antiestrogen fulvestrant for HR+, HER2- breast cancer treatment. Here, a novel bioanalytical LC-ESI-MS/MS method was developed for the quantitation of these six drugs in human plasma. The samples were prepared by simple protein precipitation followed by solvent evaporation. A Kinetex biphenyl column (150 x 4.6 mm, 2.6 mu m) used for chromatographic analysis adequately resolved even the closely eluting aromatase inhibitors' peaks. The mobile phase consisted of 0.1% formic acid in water and in ACN, in a linear gradient. An additional gradient step was added to eliminate the observed carry-over. The proposed method was fully validated in the relevant linear ranges covering the expected plasma concentrations of all six drugs (correlation coefficients between 0.9996 and 0.9931). The intra-day method precision (CV) ranged from 3.1% to 15%, while intra-day accuracy (%bias) was between -1.5% and 15.0%. The inter-day precision ranged from 1.6% to 14.9%, with accuracy between -14.3% and 14.6%, which is in accordance with the EMA and ICH guidelines on bioanalytical method validation. The method was successfully applied to samples from patients treated for HR+, HER2- breast cancer.
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