Simultaneous determination of nine tyrosine kinase inhibitors by 96-well solid-phase extraction and ultra performance
Stéphane Bouchet1, Emmanuelle Chauzit, Dominique Ducint
1Department of Clinical Pharmacology and Toxicology, Pellegrin Hospital and University Victor Segalen, 33076 Bordeaux, France. stephane.bouchet@chu-bordeaux.fr
Background:
Tyrosine Kinase Inhibitors (TKIs) are a class of targeted drugs for the treatment of malignant pathologies. The metabolic profile of these drugs can result in great interindividual variability, thus therapeutic drug monitoring (TDM) is of importance. Here, a rapid and specific method for quantification of nine TKIs in plasma samples is described.
Methods:
Chromatography was performed on a Waters Acquity-UPLC® system with BEH C18-50*2.1 mm column, under a gradient of ammonium formate-acetonitrile. An Acquity-TQD® with electrospray ionization was used for detection. Samples were prepared by solid phase extraction (Oasis® MCX μElution) and eluate was injected in the system.
Results:
Calibration curves ranged from 10 to 5000 ng/mL for imatinib, its metabolite, nilotinib, lapatinib, erlotinib and sorafenib and from 0.1 to 200 ng/mL for dasatinib, axitinib, gefitinib and sunitinib. Peaks of each compound (retention time from 0.76 to 2.51 min) were adequately separated. The mean relative extraction recovery was in the range of 90.3-106.5% thanks to the use of stable isotopes as internal standard. There was no significant ion suppression observed at the respective TKI retention times.
Conclusion:
This rapid, sensitive and specific UPLC/MS-MS method is able to perform simultaneous quantification of nine TKIs in human plasma and usable for routine TDM.
Insights
A new UPLC/MS-MS method enables rapid quantification of nine Tyrosine Kinase Inhibitors (TKIs) in plasma. This supports therapeutic drug monitoring (TDM) for targeted cancer therapies, improving patient outcomes.
Area of Science:
- Analytical Chemistry
- Pharmacology
- Oncology
Background:
- Tyrosine Kinase Inhibitors (TKIs) are crucial targeted therapies for cancers.
- Significant interindividual variability in TKI metabolism necessitates Therapeutic Drug Monitoring (TDM).
Purpose of the Study:
- To develop and validate a rapid, sensitive, and specific method for quantifying nine TKIs in human plasma.
- To facilitate routine TDM for optimizing TKI treatment.
Main Methods:
- Ultra-Performance Liquid Chromatography coupled with tandem Mass Spectrometry (UPLC/MS-MS) was employed.
- Samples underwent Solid Phase Extraction (SPE) using Oasis MCX μElution cartridges.
- Chromatography utilized a BEH C18 column with an ammonium formate-acetonitrile gradient.
Main Results:
- Simultaneous quantification of nine TKIs achieved with retention times from 0.76 to 2.51 min.
- Calibration curves spanned 0.1–5000 ng/mL, demonstrating wide dynamic range.
- High extraction recovery (90.3–106.5%) and no significant ion suppression were observed.
Conclusions:
- The developed UPLC/MS-MS method is rapid, sensitive, and specific for simultaneous TKI quantification.
- This method is suitable for routine TDM in clinical settings.
- Enables precise monitoring of TKI plasma concentrations for personalized cancer treatment.
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