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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
- Source :
- International Journal of Analytical Chemistry, International Journal of Analytical Chemistry, Vol 2019 (2019)
- Publication Year :
- 2019
- Publisher :
- Hindawi Limited, 2019.
-
Abstract
- 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.
- Subjects :
- Analyte
Accuracy and precision
lcsh:QD71-142
Chromatography
Article Subject
Formic acid
Electrospray ionization
010401 analytical chemistry
lcsh:Analytical chemistry
Tandem mass spectrometry
01 natural sciences
0104 chemical sciences
Analytical Chemistry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
chemistry
Pharmacokinetics
030220 oncology & carcinogenesis
Protein precipitation
Acetonitrile
Research Article
Subjects
Details
- ISSN :
- 16878779 and 16878760
- Volume :
- 2019
- Database :
- OpenAIRE
- Journal :
- International Journal of Analytical Chemistry
- Accession number :
- edsair.doi.dedup.....6a76674f063b7c8d271b1ecbe3d928d8