Naslov
Development and Clinical Application of a Novel DLLME-HPLC-DAD-FLD Method for the Determination of CDK4/6 Inhibitors in Patient Plasma Samples

Autori
Turković, Lu ; Mlinarić, Zvonimir ; Koraj, Natan ; Ščavničar, Andrijana ; Lovrić Mila ; Silovski, Tajana ; Sertić, Miranda

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
33rd International Symposium on Chromatography Book of Abstracts / Felinger, Attila - Budimpešta : Hungarian Society for Separation Sciences, 2022

ISBN
978-615-5270-74-1

Skup
33rd International Symposium on Chromatography

Mjesto i datum
Budimpešta, Mađarska, 18.09.2022. - 22.09.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Palbociclib ; Ribociclib ; Abemaciclib ; DLLME ; TDM

Sažetak
Cyclin D dependent kinase 4 and 6 (CDK4/6) inhibitors palbociclib (PAL), ribociclib (RIB) and abemaciclib (ABE) are novel drugs used in the treatment of HR+, HER2- breast cancer. They are undergoing additional monitoring to gain further insight into their security profiles, as well as the inter-patient pharmacokinetic variabilities. In this work, a novel, cost-effective and eco- friendly dispersive liquid-liquid microextraction (DLLME) sample preparation procedure and a HPLC- DAD-FLD method were developed for the analysis of these drugs in human plasma. The samples (100 µL) were extracted with 150 µL of the mixture of isopropanol and chloroform (1:2, v/v) as the dispersive and extracting solvents, respectively. High extraction yields (above 90%) and good sample clean-up were achieved. The chromatographic conditions include an XBridge phenyl column (150 x 4.6 mm, 3.5 µm) with methanol and water containing 0.1% formic acid in gradient elution. At a 1 mL/min flow rate and a 30 °C column temperature, the analytes eluted within 6 min. The method proved linear in the ranges of 250–6000 ng/mL for RIB, 150–4000 for PAL, and 100–2500 for ABE, thus enabling their determination in real patient plasma samples. Mean precision (% CV) of quality control samples was less than 6.7% and the accuracy (% bias) was less than 1.5% for all analytes. The method was successfully applied for the quantitation of the drugs of interest in real patient plasma samples. In comparison to other previously published methods, this approach utilises a novel plasma sample preparation procedure and ensures adequate quantitation limits using easily accessible detectors. This work has been fully supported by the Croatian Science Foundation, under the project number UIP- 2019-04-8461 and DOK-2021-02-4595.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Kliničke medicinske znanosti, Farmacija

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