Simultaneous Quantification of Brigatinib and Brigatinib-Analog in Rat Plasma and Brain Homogenate by LC-MS/MS: Application to Comparative Pharmacokinetic and Brain Distribution Studies

Brigatinib and brigatinib-analog are potent and selective ALK inhibitors with the similar structure. A simple and sensitive high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of brigatinib and brigatinib-analog in rat plasma and brai...

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Main Authors: Bo Li, Min Lu, Lei Jin, Maoen Zheng, Peilu Sun, Shanshan Lei, Shan Xiong, Suhong Chen
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:International Journal of Analytical Chemistry
Online Access:http://dx.doi.org/10.1155/2019/9028309
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author Bo Li
Min Lu
Lei Jin
Maoen Zheng
Peilu Sun
Shanshan Lei
Shan Xiong
Suhong Chen
author_facet Bo Li
Min Lu
Lei Jin
Maoen Zheng
Peilu Sun
Shanshan Lei
Shan Xiong
Suhong Chen
author_sort Bo Li
collection DOAJ
description Brigatinib and brigatinib-analog are potent and selective ALK inhibitors with the similar structure. A simple and sensitive high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of brigatinib and brigatinib-analog in rat plasma and brain homogenate was developed and validated. Chromatographic separation was carried out on an ODS column with acetonitrile and 0.1% formic acid in water as the mobile phase with gradient elution at a flow rate of 0.5 mL/min. Detections were performed using a TSQ Quantum Ultra mass spectrometric detector with electrospray ionization (ESI) interface, which was operated in the positive ion mode. A simple protein precipitation preparation process was used. The lower limits of quantification (LLOQs) were 1.0 ng/mL and 0.5 ng/mL for analytes in rat plasma and brain homogenate, respectively. The intrabatch and interbatch precision and accuracy of brigatinib and brigatinib-analog were well within the acceptable limits of variation. The simple and sensitive LC-MS/MS method was successfully applied to the pharmacokinetic and brain distribution studies following a single oral administration of brigatinib and brigatinib-analog to rats. The above studies would lay a good foundation for the further applications of brigatinib and brigatinib-analog.
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series International Journal of Analytical Chemistry
spelling doaj-art-e1ae770a96f04e6aaeb4ea36e5ee46a32025-02-03T05:53:19ZengWileyInternational Journal of Analytical Chemistry1687-87601687-87792019-01-01201910.1155/2019/90283099028309Simultaneous Quantification of Brigatinib and Brigatinib-Analog in Rat Plasma and Brain Homogenate by LC-MS/MS: Application to Comparative Pharmacokinetic and Brain Distribution StudiesBo Li0Min Lu1Lei Jin2Maoen Zheng3Peilu Sun4Shanshan Lei5Shan Xiong6Suhong Chen7Zhejiang University of Technology, Hangzhou 310014, ChinaSchool of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan 250200, ChinaDepartment of Pharmaceutical Engineering, Shandong Drug and Food Vocational College, Weihai 264210, ChinaShandong Laboratory Animal Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250002, ChinaInstitute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250062, ChinaZhejiang University of Technology, Hangzhou 310014, ChinaInstitute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250062, ChinaZhejiang University of Technology, Hangzhou 310014, ChinaBrigatinib and brigatinib-analog are potent and selective ALK inhibitors with the similar structure. A simple and sensitive high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of brigatinib and brigatinib-analog in rat plasma and brain homogenate was developed and validated. Chromatographic separation was carried out on an ODS column with acetonitrile and 0.1% formic acid in water as the mobile phase with gradient elution at a flow rate of 0.5 mL/min. Detections were performed using a TSQ Quantum Ultra mass spectrometric detector with electrospray ionization (ESI) interface, which was operated in the positive ion mode. A simple protein precipitation preparation process was used. The lower limits of quantification (LLOQs) were 1.0 ng/mL and 0.5 ng/mL for analytes in rat plasma and brain homogenate, respectively. The intrabatch and interbatch precision and accuracy of brigatinib and brigatinib-analog were well within the acceptable limits of variation. The simple and sensitive LC-MS/MS method was successfully applied to the pharmacokinetic and brain distribution studies following a single oral administration of brigatinib and brigatinib-analog to rats. The above studies would lay a good foundation for the further applications of brigatinib and brigatinib-analog.http://dx.doi.org/10.1155/2019/9028309
spellingShingle Bo Li
Min Lu
Lei Jin
Maoen Zheng
Peilu Sun
Shanshan Lei
Shan Xiong
Suhong Chen
Simultaneous Quantification of Brigatinib and Brigatinib-Analog in Rat Plasma and Brain Homogenate by LC-MS/MS: Application to Comparative Pharmacokinetic and Brain Distribution Studies
International Journal of Analytical Chemistry
title Simultaneous Quantification of Brigatinib and Brigatinib-Analog in Rat Plasma and Brain Homogenate by LC-MS/MS: Application to Comparative Pharmacokinetic and Brain Distribution Studies
title_full Simultaneous Quantification of Brigatinib and Brigatinib-Analog in Rat Plasma and Brain Homogenate by LC-MS/MS: Application to Comparative Pharmacokinetic and Brain Distribution Studies
title_fullStr Simultaneous Quantification of Brigatinib and Brigatinib-Analog in Rat Plasma and Brain Homogenate by LC-MS/MS: Application to Comparative Pharmacokinetic and Brain Distribution Studies
title_full_unstemmed Simultaneous Quantification of Brigatinib and Brigatinib-Analog in Rat Plasma and Brain Homogenate by LC-MS/MS: Application to Comparative Pharmacokinetic and Brain Distribution Studies
title_short Simultaneous Quantification of Brigatinib and Brigatinib-Analog in Rat Plasma and Brain Homogenate by LC-MS/MS: Application to Comparative Pharmacokinetic and Brain Distribution Studies
title_sort simultaneous quantification of brigatinib and brigatinib analog in rat plasma and brain homogenate by lc ms ms application to comparative pharmacokinetic and brain distribution studies
url http://dx.doi.org/10.1155/2019/9028309
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