Naslov
Development and validation of a novel LC-MS/MS method for the simultaneous determination of abemaciclib, palbociclib, ribociclib, anastrozole, letrozole, and fulvestrant in plasma samples: a prerequisite for personalized breast cancer treatment

Autori
Turković, Lu ; Bočkor, Luka ; Ekpenyong, Oscar ; Silovski, Tajana ; Lovrić, Mila ; Crnković, Slaven ; Nigović, Biljana ; Sertić, Miranda

Izvornik
Pharmaceuticals (1424-8247) 15 (2022), 5; 614, 19

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
CDK4/6 inhibitors ; breast cancer ; palbociclib ; ribociclib ; abemaciclib ; anastrozole ; letrozole ; fulvestrant ; therapeutic drug monitoring ; LC-MS

Sažetak
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 × 4.6 mm, 2.6 μm) 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.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti, Farmacija

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