An Accurate and Effective Method for Measuring Osimertinib by UPLC-TOF-MS and Its Pharmacokinetic Study in Rats

Dong, Songtao; Liu, Ying; Huang, Yang; Wu, Yin; Ding, Cong-Yang; Lu, Meng; Dong, Zhanjun; Zhang, Yuan

doi:10.3390/molecules23112894

Cited by 10 publications

(8 citation statements)

References 20 publications

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“…A sample: ACN ratio of 1 : 4 resulted in a promising recovery of osimertinib and IS. One hundred μ L of rat plasma was prepared for sample preparation as Dong described [ 14 ]. Many blood samples from each rat were collected for the pharmacokinetic study, which may influence the physiological and functional characteristics of rats.…”

Section: Resultsmentioning

confidence: 99%

“…Many blood samples from each rat were collected for the pharmacokinetic study, which may influence the physiological and functional characteristics of rats. In addition, the supernatant was evaporated to dryness through nitrogen gas for sample preparation which was time-consuming and tedious [ 14 ]. Protein precipitation method was chosen in our experiment, and the method was simple and fast.…”

Section: Resultsmentioning

confidence: 99%

“…Compared with nominal concentration, RSD of LLOQ and QC concentration were less than 15%, and the accuracy was within 85%–115%. The intra- and interday precision and accuracy assays only investigated LQC, MQC, and HQC concentrations as Dong described [ 14 ]. According to the Bioanalytical Method Validation Guidance of FDA, the precision and accuracy assays should be validated with four QC levels per run (LLOQ, LQC, MQC, and HQC) and should be ±20% of nominal concentration at LLOQ [ 15 ].…”

Section: Resultsmentioning

confidence: 99%

“…An appropriate analytical method should be established for evaluating the drug interaction between Rg3 and osimertinib. However, to the best of our knowledge, there were only two published articles about liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for determination of osimertinib in rat plasma [ 13 , 14 ]. There were some drawbacks in these methods such as being time-consuming, tedious sample preparation, and high sample volume (100 μ L), which was not adequate for pharmacokinetic studies.…”

Section: Introductionmentioning

confidence: 99%

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An UPLC-MS/MS Method for Determination of Osimertinib in Rat Plasma: Application to Investigating the Effect of Ginsenoside Rg3 on the Pharmacokinetics of Osimertinib

Ying

Wei

Liu

et al. 2020

International Journal of Analytical Chemistry

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Osimertinib is a novel oral, potent, and irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for treatment of advanced T790M mutation-positive advanced non-small cell lung cancer, which is commonly combined with ginsenoside Rg3 in clinic to enhance the efficacy and minimize adverse reactions. In the present study, a highly sensitive UPLC-MS/MS method was established and validated for analysis of osimertinib in rat plasma according to US FDA guideline. Separation was performed on a C18 (2.1 × 50 mm, 2.6 μm) column using a gradient elution of ammonium formate (10 mM) with 0.1% formic acid buffer (A) and ACN (B) at a flow rate of 0.2 mL/min. Detection was carried out on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization in the MRM mode. The method was validated over a concentration range of 1–400 ng/mL for osimertinib. The intra- and interday accuracy and precision values were within ±15%. No significant degradation occurred under the experimental conditions in stability assays. There was a further investigation on the effects of multiple doses of ginsenoside Rg3 on the pharmacokinetics of osimertinib in rats for the first time. The results implied that osimertinib exhibited a slow absorption and moderate-rate elimination in rats following oral administration. Coadministeration with ginsenoside Rg3 (5 mg/kg, 7 days, i.g.) may have no effect on the pharmacokinetics of osimertinib in rats. The results provide a reference for the clinical concomitant medications of Rg3 and osimertinib.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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An UPLC-MS/MS Method for Determination of Osimertinib in Rat Plasma: Application to Investigating the Effect of Ginsenoside Rg3 on the Pharmacokinetics of Osimertinib

Ying

Wei

Liu

et al. 2020

International Journal of Analytical Chemistry

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“…The determination of the concentration of osimertinib in biological samples has been evaluated only recently. Osimertinib could be measured alone or simultaneously with other TKIs by LC-MS/MS [93,103,104,117,118]. The results reported contrasting data on osimertinib’s stability in plasma.…”

Section: Applications For Routine Egfr-tki Dosagementioning

confidence: 99%

FDA- and EMA-Approved Tyrosine Kinase Inhibitors in Advanced EGFR-Mutated Non-Small Cell Lung Cancer: Safety, Tolerability, Plasma Concentration Monitoring, and Management

2019

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Non-small-cell lung cancer (NSCLC) is the most common form of primary lung cancer. The discovery of several oncogenic driver mutations in patients with NSCLC has allowed the development of personalized treatments based on these specific molecular alterations, in particular in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene. Gefitinib, erlotinib, afatinib, and osimertinib are TK inhibitors (TKIs) that specifically target EGFR and are currently approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) as first line treatment for sensitive EGFR-mutant patients. However, these four drugs are associated with severe adverse events (AEs) that can significantly impact patient health-related quality of life and patient monitoring. EGFR-TKIs are commonly used together with other types of medication that can substantially interact. Here, we review approaches used for the management of TKI-AEs in patients with advanced NSCLC to promote the benefits of treatments and minimize the risk of TKI treatment discontinuation. We also consider potential TKI–drug interactions and discuss the usefulness of plasma concentration monitoring TKIs based on chromatographic and mass spectrometry approaches to guide clinical decision-making. Adjusting the most appropriate therapeutic strategies and drug doses may improve the performance therapy and prognosis of patients with advanced EGFR-mutated NSCLC.

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An accurate, rapid, and sensitive method for simultaneous determination of four typical heterocyclic amines in roasted pork patties: Application in the study of inhibitory effects of astaxanthin

Yan

Zhang

Yang

et al. 2021

J of Separation Science

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Heterocyclic aromatic amines, as a group of mutagenic and carcinogenic compounds, have gained worldwide concern. In this study, an accurate, rapid, and sensitive confirmation and quantification method of four major heterocyclic aromatic amines in roasted pork was developed based on Q-Orbitrap along with Quick, Easy, Cheap, Effective, Rugged, and Safe extraction. The limit of detections and limit of quantitations were found to be 0.2-1.2 μg/kg and 0.6-3.5 μg/kg, respectively, revealing the high sensitivity of this method. Obtained results showed recoveries ranging from 78.1 to 97.4%, depending on the different heterocyclic aromatic amines and spiked levels. Precision was in the range of 2.6-4.5% for four heterocyclic aromatic amines at different levels. In addition, the developed method had been applied to investigate the inhibitory effects of astaxanthin on the above-mentioned heterocyclic aromatic amines in roasted pork. The amount of astaxanthin with the best inhibitory effects was 7.5 mg (0.0375%), which led to significant reduction in heterocyclic aromatic amines levels over 50%.

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An Accurate and Effective Method for Measuring Osimertinib by UPLC-TOF-MS and Its Pharmacokinetic Study in Rats

Cited by 10 publications

References 20 publications

An UPLC-MS/MS Method for Determination of Osimertinib in Rat Plasma: Application to Investigating the Effect of Ginsenoside Rg3 on the Pharmacokinetics of Osimertinib

An UPLC-MS/MS Method for Determination of Osimertinib in Rat Plasma: Application to Investigating the Effect of Ginsenoside Rg3 on the Pharmacokinetics of Osimertinib

FDA- and EMA-Approved Tyrosine Kinase Inhibitors in Advanced EGFR-Mutated Non-Small Cell Lung Cancer: Safety, Tolerability, Plasma Concentration Monitoring, and Management

An accurate, rapid, and sensitive method for simultaneous determination of four typical heterocyclic amines in roasted pork patties: Application in the study of inhibitory effects of astaxanthin

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