Abstract Liquid chromatography tandem mass spectrometry (LC-MS/MS) is used routinely in clinical diagnostics; however, automating the sample pretreatment is challenging. We established and evaluated an automated method based on the magnetic bead  extraction principle (MBE) to measure normetanephrine (NMN), metanephrine (MN), and 3-methoxytyramine (3-MT).  The target analytes were extracted, purifed, and concentrated using diferent solvents and chemical bond–modifed magnetic beads transferred via a magnetic bar. The linearity, recovery, matrix efect, and precision of MBE were evaluated  thoroughly, and compared with traditional solid-phase extraction (SPE) using 131 plasma samples. The chromatography  peaks of metanephrines and 3-MT, extracted via MBE, are symmetrical, without interfering peaks. The linearity was excellent with correlation coefcient (r) > 0.99. The MBE exhibited good reproducibility with within-run coefcient variations  (CVs) of 1.96–2.00%, 4.06–5.75%, and 3.89–4.90% for MN, NMN, and 3-MT, respectively. The total CVs for MN, NMN,  and 3-MT were 1.96–2.80%, 5.12–5.75%, and 5.44–6.27%, respectively. The relative recoveries for MN, NMN, and 3-MT  varied between 93.5 and 107.4%, whereas their biases were all within 10%. The results for MN, NMN, and 3-MT extracted  via MBE compared with SPE exhibited excellent correlation, with r > 0.99; the mean bias% for MN, NMN, and 3-MT  were small (−2.9%, −3.2%, and −3.2%, respectively). In conclusion, the automated MBE method for measuring plasma  metanephrines and 3-MT can be applied in future routine clinical diagnostics, and the MBE principle may indicate a new  era for LC-MS/MS in clinical application. 

Keywords LC/MS · Catecholamines · Sample preparation · Magnetic bead extraction · Plasma