Ultrasonic-assisted magnetic sorbent-wrapped stick dip extraction enables batch-scale and green LC-MS/MS analysis of tyrosine kinase inhibitors in plasma.

A novel ultrasound-assisted magnetic sorbent-wrapped stick dip extraction (UA-MSWS-DE) method was developed for the batch-scale determination of seven tyrosine kinase inhibitors (TKIs) in human plasma. The extraction device was fabricated by immobilizing octadecylphosphonic acid-functionalized magnetic nanoparticles onto flame-sealed glass capillaries embedded with magnets. Ultrasonic-assisted dip extraction was used to extract TKIs from diluted plasma, followed by quantification via liquid chromatography-tandem mass spectrometry (LC-MS/MS). Key extraction parameters were systematically optimized, yielding the following optimal conditions: sample pH 5.0 and volume 1.0 mL, sorbent particle size 20 nm and dosage 10 mg, extraction time 20 min, and desorption with 150 µL of ethanol for 8 min. The method demonstrated excellent linearity (R2 ≥ 0.99), low limits of quantification (0.1-5.0 ng/mL), and good intra-/inter-day precision (RSDs < 14.95%). The accuracy in blinded plasma samples, tested at 0.25-25% of the studied concentration range, ranged from 87.13 to 112.33%. Compared to conventional magnetic dispersive solid-phase extraction, the UA-MSWS-DE strategy simplifies handling and is designed to facilitate potential parallel processing using only an ultrasonic bath. Five greenness metrics confirmed the method's high sustainability. Furthermore, the modular design enables adaptation to other analytes by modifying the sorbent coating, making UA-MSWS-DE a sensitive, green, and automation-ready method for therapeutic drug monitoring.