Naslov
Evaluation of extraction efficacy and matrix effects for six anticancer drugs in human plasma using different sample preparation techniques with LC-MS

Autori
Turković, Lu ; Papić, Martina ; Mlinarić, Zvonimir ; Silovski, Tajana ; Sertić, Miranda

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

Izvornik
28th Croatian Meeting of Chemists and Chemical Engineers Book of Abstracts / Rogošić, Marko - Zagreb : Hrvatsko društvo kemijskih inženjera i tehnologa (HDKI), 2023, 137-137

Skup
28th Croatian Meeting of Chemists and Chemical Engineers

Mjesto i datum
Rovinj, Hrvatska, 28.03.2023. - 31.03.2023

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
bioanalysis ; sample preparation ; LC-MS ; breast cancer

Sažetak
Determination of matrix effects and extraction recoveries is of high importance in bioanalytical method development. Matrix effects are commonly observed in LC-MS analyses of human plasma samples as signal enhancement or suppression due to co- extracted plasma components. Complicated sample preparation procedures are employed to reduce interferences and selectively extract analytes of interest from complex and variable matrices [1]. Palbociclib (PAL), ribociclib (RIB), abemaciclib (ABE), anastrozole (ANA), letrozole (LET), and fulvestrant (FUL) are anticancer drugs used in combination therapy of breast cancer. They are prone to inter-patient concentration variability and are potential candidates for therapeutic drug monitoring, therefore several LC-MS methods for their quantitation in patient plasma samples have been reported [2-3]. However, little attention has been given to developing a robust sample preparation procedure for the simultaneous extraction of these drugs, which exhibit a wide range of physical-chemical properties that pose a challenge to their successful extraction. The aim of this work was to evaluate extraction efficacy and matrix effects using protein precipitation (PPT), solid phase extraction (SPE) with different sorbents and eluents, phospholipid removal (PLR), and dispersive liquid-liquid microextraction (DLLME). Samples were prepared as pre-extraction and post-extraction spiked plasma and analysed using LC-MS along with standard samples of equal concentrations. Significant matrix effects and low extraction recoveries were observed for the highly lipophilic, weakly acidic FUL in most of the tested conditions. The weakly basic and relatively hydrophilic ABE suffered from extensive matrix effects with C18 sorbents, while PAL and RIB exhibited ion enhancement with mixed-mode cation exchange. Finally, the neutral and moderately lipophilic ANA and LET gave high yields with low matrix effects in most of the tested conditions except for mixed-mode cation exchange. Favourable results in terms of both extraction recoveries and matrix effects for all the analytes were obtained with DLLME using chloroform as extracting and i- propanol as dispersing solvent. Extraction recoveries were 67.3 – 94.9%, with matrix effects 46.6 – 120.4%. SPE using a C18 sorbent eluted with 5% ammonia in methanol also showed promising results, with extraction recoveries 37.5 – 100.7%, and matrix effects 88.3 – 136.4%. This work has been fully supported by the Croatian Science Foundation through projects UIP-2019-04- 8461 and DOK-2021-02-4595, and the European Regional Development Fund, project Farminova, KK.01.1.1.02.0021.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA