Related Experiment Video
Updated: Feb 17, 2026
Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
Published on: September 19, 2018
High throughput routine determination of 17 tyrosine kinase inhibitors by LC-MS/MS
Camille Merienne1, Marine Rousset1, Dominique Ducint2
1CHU de Bordeaux, Bordeaux, F-33000, France; Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, Team PHARMACOEPIDEMIOLOGY, UMR 1219, F-33000 Bordeaux, France.
Abstract:
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: 0.1-200ng/ml, 1-200ng/ml, 4-800ng/ml and 25-5000ng/ml. Solid phase extraction was used and separation was performed with HPLC using a gradient system on a solid core particle C18 column (5×2.1mm, 1.6μm). Ions were detected with a triple quadrupole mass spectrometry system. This assay allows rapid determination of 19 TKI in less than 5min per run. This high throughput routine method will be useful to adjust doses of oral anticancer drugs in order to improve treatments efficacy.
Insights
Therapeutic drug monitoring of tyrosine kinase inhibitors (TKIs) can enhance cancer treatment. A new analytical method rapidly quantifies 19 TKIs in plasma, aiding dose adjustments for improved efficacy.
Area of Science:
- Pharmacology
- Analytical Chemistry
- Oncology
Background:
- Therapeutic drug monitoring (TDM) of tyrosine kinase inhibitors (TKIs) is crucial for optimizing cancer therapy.
- Existing methods may not offer the high throughput required for routine clinical application.
Purpose of the Study:
- To develop and validate a rapid analytical method for quantifying multiple TKIs and their metabolites in human plasma.
- To establish a high-throughput assay for TKI drug monitoring to support personalized cancer treatment.
Main Methods:
- Quantification of 19 TKIs and 2 metabolites using solid-phase extraction and High-Performance Liquid Chromatography (HPLC) with a C18 column.
- Detection via triple quadrupole mass spectrometry (MS/MS).
- Assay designed for rapid analysis, with run times under 5 minutes per sample.
Main Results:
- The developed assay successfully quantifies 19 TKIs and 2 metabolites across various concentration ranges.
- Achieved rapid determination of TKI levels in human plasma, with high throughput capabilities.
- The method demonstrates suitability for routine clinical laboratory use.
Conclusions:
- A novel, rapid, and high-throughput analytical method for TKI quantification in plasma has been established.
- This assay facilitates therapeutic drug monitoring, enabling precise dose adjustments for oral anticancer drugs.
- The method holds significant potential for improving treatment efficacy and patient outcomes in oncology.
