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 language | English (US) |
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Article number | 114436 |
Journal | Journal of Pharmaceutical and Biomedical Analysis |
Volume | 208 |
DOIs | |
State | Published - Jan 20 2022 |
Keywords
- Assay
- Tandem mass spectrometry
- Validation
- Vistusertib
ASJC Scopus subject areas
- Drug Discovery
- Analytical Chemistry
- Spectroscopy
- Clinical Biochemistry
- Pharmaceutical Science