Quantitation of Vistusertib by UHPLC-MS/MS in Rat Plasma and its Application to a Pharmacokinetic Study

Abstract

Aim: The present study aimed to develop a UHPLC-MS/MS method for determination of vistusertib in biological matrix, and to describe the pharmacokinetic behavior of vistusertib in SD rats. Methodology & results: After protein precipitation with acetone and acetonitrile (1:1), the chromatographic separation was achieved on an Agilent Poroshell 120 EC-C₁₈ column and detected with a SCIEX QTRAP 4500 mass spectrometer under positive ionization mode. The developed UHPLC-MS/MS method showed an excellent linearity within the range of 1.0–3000ng/ml with good accuracy and precision. Vistusertib showed a rapid absorption and reached the maximum concentration of 3532.2±678.0ng/ml 20–30min after oral administration in Sprague-Dawley rats. Conclusion: The established analytical method was fast, sensitive and robust, and successfully applied to describe the pharmacokinetic behavior of vistusertib following an oral administration in rats.

Keywords:

• mTORC inhibitor
• pharmacokinetics
• UHPLC-MS/MS
• Vistusertib

Financial & competing interests disclosure

This research was financially supported by Education Department of Liaoning Province (2019LCJ08), Young and Middle Aged Teachers' Career Development Support Project of Shenyang Pharmaceutical University (ZQN2019005). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that the animal study was performed in accordance with the Guideline for Animal Experimentation of Shenyang Pharmaceutical University, and the protocol was approved by the Animal Ethics Committee of the Institution.