Performance Comparison of Liquid Chromatography and Paper Spray Ionization with Mass Spectrometry for Measuring Kinase Inhibitors in Human Plasma

• DOI: 10.1021/acsptsci.4c00646
• Publication Date: 2025-01-16T23:09:01Z
• Authors: Richard G. Lahr; Makenzie Meyer; Leah Nelson; Lisa A. Kottschade; Paul J. Jannetto; Yifei K. Yang

Kinase inhibitors are small-molecule drugs designed to target oncogenic mutations in cancer treatment. Although less toxic than conventional chemotherapy drugs, they can cause severe adverse effects some patients, resulting dose reduction and cessation. To evaluate if therapeutic drug monitoring of kinase their metabolites improve toxicity assessment we developed evaluated the analytical performance two parallel methods utilizing liquid chromatography (LC) paper spray (PS) ionization coupled with a triple quadrupole mass spectrometer (MS) for measurement dabrafenib, its major metabolite OH-dabrafenib, trametinib patient plasma samples. The PS-MS method yielded faster sample analysis time (2 min) compared LC separation (9 min). shared same range (AMR) dabrafenib OH-dabrafenib (10-3500 10-1250 ng/mL), but AMR differed (LC-MS: 0.5-50 ng/mL; PS-MS: 5.0-50 ng/mL). imprecision across respective was 1.3-6.5% (dabrafenib), 3.0-9.7% (OH-dabrafenib), 1.3-5.1% (trametinib) LC-MS 3.8-6.7% 4.0-8.9% 3.2-9.9% method. Using authentic samples, quantification results were comparable between methods: (correlation coefficient r = 0.9977), (r 0.885), 0.9807). Nonetheless, displayed significantly higher variations Based on method, able profile concentrations metabolism patterns patients who receiving BRAF V600 mutation-driven malignancies.