High throughput routine determination of 17 tyrosine kinase inhibitors by LC-MS/MS

Several studies have shown that therapeutic drug monitoring of tyrosine kinase inhibitors (TKI) can improve their benefit in cancer. An analytical tool has been developed in order to quantify 17 tyrosine kinase inhibitors and 2 metabolites in human plasma (afatinib, axitinib, bosutinib, crizotinib, dabrafenib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, ponatinib, regorafenib, regorafenib M2, regorafenib M5, ruxolitinib, sorafenib, sunitinib, vandetanib). Drugs were arranged in four groups, according to their plasma concentration range: 0.1-200 ng/ml, 1-200 ng/ml, 4-800 ng/ml and 25-5000 ng/ml. Solid phase extraction was used and separation was performed with HPLC using a gradient system on a solid core particle C18 column (5 × 2.1 mm, 1.6 μm). Ions were detected with a triple quadrupole mass spectrometry system. This assay allows rapid determination of 19 TKI in less than 5 min per run. This high throughput routine method will be useful to adjust doses of oral anticancer drugs in order to improve treatments efficacy.