Validation of a rapid liquid chromatography tandem mass spectrometric method for the quantitative analysis of vistusertib

Susan C. Scott, Nicole M. Anders, Morgan Scardina, Christine L. Hann, Michelle A. Rudek

Research output: Contribution to journalArticlepeer-review

Abstract

Vistusertib is an orally bioavailable mTOR inhibitor that is being studied in clinical trials. A novel reliable method was developed to quantitate vistusertib using LC-MS/MS to explore drug exposure-response relationships. Sample preparation involved protein precipitation using acetonitrile. Separation of vistusertib and the internal standard, AZD8055, was achieved with a Waters Acquity UPLC BEH C18 column utilizing isocratic elution over a 3 min total analytical run time. A SCIEX 4500 triple quadrupole mass spectrometer operated in positive electrospray ionization mode was used for the detection of vistusertib. The assay range was 5–5000 ng/mL and proved to be accurate (98.7–105.7%) and precise (CV ≤ 10.5%). A 40,000 ng/mL sample that was diluted 1:10 (v/v) with plasma was accurately quantitated. Long-term frozen plasma stability for vistusertib at −70 °C has been determined for at least 29 months. The method was applied for the measurement of plasma concentrations of vistusertib in a patient a solid tumor receiving 35 mg twice daily dose orally.

Original languageEnglish (US)
Article number114436
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume208
DOIs
StatePublished - Jan 20 2022

Keywords

  • Assay
  • Tandem mass spectrometry
  • Validation
  • Vistusertib

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

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