Validated extended multiplexed LC-MS/MS assay for the quantification of adagrasib and sotorasib in human plasma, together with four additional SMIs

Paul D Kruithof, Yvo M de Beer, Judith L Gulikers, Leo M L Stolk, Lizza E L Hendriks, Sander Croes, Robin M J M van Geel*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Recently, two small molecular inhibitors (SMIs) -adagrasib and sotorasib- have been introduced for targeting Kirsten rat sarcoma (KRAS) p.G12C mutations in patients with non-small cell lung cancer (NSCLC). In order to support pharmacokinetic research as well as clinical decision making, we developed and validated a simple and accurate liquid chromatography-tandem mass spectrometry method for the multiplexed quantification of adagrasib and sotorasib. This assay was co-validated with the quantification for brigatinib, lorlatinib, pralsetinib and selpercatinib. Methanol was used for single-step protein precipitation. Chromatographic separation was performed using an Acquity® HSS C18 UPLC column, with an elution gradient of ammonium formate 0.1 % / in water and acetonitrile. In K2-EDTA plasma, adagrasib was found to be stable for at least seven days at room temperature and 4 °C, and at least 3 months at -80 °C. Sotorasib was found to be stable for at least three days at room temperature, seven days at 4 °C and at least 3 months at -80 °C. The method was validated over a linear range of 80-4000 ng/mL for adagrasib and 25-2500 ng/mL for sotorasib. The assay is therefore well-equipped for determining plasma concentrations in clinical practice.
Original languageEnglish
Article number123918
Number of pages7
JournalJournal of chromatography. B, Analytical technologies in the biomedical and life sciences
Volume1231
Issue number1
DOIs
Publication statusPublished - 1 Dec 2023

Keywords

  • Adagrasib
  • Non-Small Cell Lung Cancer
  • Pharmacokinetics
  • Sotorasib
  • Validation

Fingerprint

Dive into the research topics of 'Validated extended multiplexed LC-MS/MS assay for the quantification of adagrasib and sotorasib in human plasma, together with four additional SMIs'. Together they form a unique fingerprint.

Cite this