Electromembrane extraction of anthracyclines from plasma: Comparison with conventional extraction techniques

Area of Science:

• Analytical Chemistry
• Pharmacokinetics
• Biotechnology

Background:

• Anthracyclines (ANT) are crucial chemotherapy drugs, but their analysis in biological matrices like plasma is challenging due to complex matrices.
• Conventional sample preparation methods, such as protein precipitation (PP) and liquid-liquid extraction (LLE), often suffer from low recovery, significant matrix effects, and phospholipid contamination.
• Developing a robust and efficient extraction technique for ANT is essential for accurate pharmacokinetic studies and therapeutic drug monitoring.

Purpose of the Study:

• To investigate and optimize Electromembrane Extraction (EME) for the extraction of polar zwitterionic anthracyclines (ANT) from rabbit plasma.
• To compare the performance of EME against conventional methods (PP and LLE) regarding extraction reliability, recovery, and matrix effects.
• To evaluate the phospholipids profile in EME extracts and assess the practical applicability of EME in a biological context.

Main Methods:

• Electromembrane extraction (EME) was optimized for the simultaneous extraction of doxorubicin, daunorubicin, and daunorubicinol from rabbit plasma.
• The optimized EME method was compared with protein precipitation (PP) and liquid-liquid extraction (LLE).
• Ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) using electrospray ionization in positive ion mode was employed for analysis.

Main Results:

• EME demonstrated high extraction recovery (over 80%) and excellent sample clean-up for all tested ANT, with matrix effects of 100 ± 10% and RSD values below 4%.
• Negligible amounts of phospholipids were detected in EME extracts, indicating superior matrix simplification compared to PP and LLE.
• Validation was performed within the 0.25-1000 ng/mL range, showing method robustness.
• Consistent results were obtained when comparing EME with LLE in a pilot in vivo study, confirming EME's high reliability.

Conclusions:

• Electromembrane extraction (EME) is a simple, rapid, and repeatable technique for extracting anthracyclines from plasma.
• EME offers a significant advantage over conventional methods (PP, LLE) due to its high recovery, minimal matrix effects, and reduced phospholipid contamination.
• EME is a viable and up-to-date alternative for routine sample preparation in the analysis of anthracyclines and potentially other polar zwitterionic drugs.