Abstract

Osimertinib, a new-generation inhibitor of the epidermal growth factor, has been used for the clinical treatment of advanced T790M mutation-positive tumors. In this research, an original analysis method was established for the quantification of osimertinib by ultra-performance liquid chromatography with time of flight mass spectrometry (UPLC-TOF-MS) in rat plasma. After protein precipitation with acetonitrile and sorafinib (internal standard, IS), they were chromatographed through a Waters XTerra MS C18 column. The mobile phase was acetonitrile and water (including 0.1% ammonia). The relative standard deviation (RSD) of the intra- and inter-day results ranged from 5.38 to 9.76% and from 6.02 to 9.46%, respectively, and the extraction recovery and matrix effects were calculated to range from 84.31 to 96.14% and from 91.46 to 97.18%, respectively. The results illustrated that the analysis method had sufficient specificity, accuracy and precision. Meanwhile, the UPLC-TOF-MS method for osimertinib was successfully applied into the pharmacokinetics of SD rats.

Highlights

  • IntroductionThere areare some advantages of UPLC-MS/MS, including its high sensitivity, high stability, and short analytic time

  • Molecules 2018, 23, 2894; doi:10.3390/molecules23112894 www.mdpi.com/journal/moleculesMolecules 2018, 23, x FOR PEER REVIEW Figure1

  • ToTo thethe best of of ourour knowledge, several papers have established thethe methods forfor thethe determination of osimertinib in biological samples, and the utilized apparatuses are all ultra-performance liquid of osimertinib in biological samples, and the utilized apparatuses are all ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS)

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Summary

Introduction

There areare some advantages of UPLC-MS/MS, including its high sensitivity, high stability, and short analytic time. Advantages of UPLC-MS/MS, including its high sensitivity, high stability, and short analytic time. To methods date, methods using UPLC-TOF-MS the determination of osimertinib onso [18]. To date, using UPLC-TOF-MS for the for determination of osimertinib have been reported. In the present are the to quantify osimertinib in rat plasma using UPLC-TOF-MS. The objective this studywas wastotoinvestigate investigateaaspecific, specific, sensitive, sensitive, rapid and reliable. UPLC-TOFmethod for osimertinib quantification in rat plasma samples. MS method for osimertinib quantification in rat samples. We have successfully investigated pharmacokinetic study osimertinib rats using this method. Investigated thethe pharmacokinetic study of of osimertinib in in rats using this

UPLC-TOF-MS Method Development
Specificity and Selectivity
Precision and Accuracy
Extraction Recovery and Matrix Effect
Stability
Pharmacokinetic Application
Drugs and Materials
Apparatus
Solution Preparation
UPLC-TOF-MS Condition
Sample Preparation
Method Validation
Linearity and Sensitivity
Data Analysis
Conclusions
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