A novel LC-MS-MS method with an effective antioxidant for the determination of edaravone, a free-radical scavenger in dog plasma and its application to a pharmacokinetic study

Shao, Feng, Hu, Xiao-ling, Liu, Xin and Shan, Mang-ting (2017) A novel LC-MS-MS method with an effective antioxidant for the determination of edaravone, a free-radical scavenger in dog plasma and its application to a pharmacokinetic study. Journal of Chromatographic Science, 55 6: 595-602. doi:10.1093/chromsci/bmx012


Author Shao, Feng
Hu, Xiao-ling
Liu, Xin
Shan, Mang-ting
Title A novel LC-MS-MS method with an effective antioxidant for the determination of edaravone, a free-radical scavenger in dog plasma and its application to a pharmacokinetic study
Journal name Journal of Chromatographic Science   Check publisher's open access policy
ISSN 0021-9665
1945-239X
Publication date 2017-07-01
Sub-type Article (original research)
DOI 10.1093/chromsci/bmx012
Open Access Status Not yet assessed
Volume 55
Issue 6
Start page 595
End page 602
Total pages 8
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Abstract The objective of this study was to investigate the stability of edaravone in dog plasma by using an added antioxidant stabilizer, with an ultimate goal of developing and validating a sensitive, reliable and robust LC-MS-MS method for determination of edaravone in plasma samples. Edaravone was unstable in plasma, but it presented a good stability performance in the plasma with sodium metabisulfite (SMB), an effective antioxidant. The blood sample was collected in the heparinized eppendorf tube containing SMB and plasma sample was deproteinized using acetonitrile containing 20 ng/mL of phenacetin (Internal standard). The chromatographic separation was performed on a Zorbax Extend-C18 analytical column (2.1 mm × 150 mm I.D., particle size 3.5 µm, Agilent Technologies, USA). The mobile phase consisted of 0.1% formic acid in water (v/v) and methanol, and gradient elution was used. The analyte detection was performed on a triple quadrupole tandem mass spectrometer equipped with positive-ion electrospray ionization by multiple reaction ion monitoring mode of the transitions at m/z [M + H]+ 175.1 → 77.1 for edaravone, and m/z [M + H]+ 180.2 → 110.0 for phenacetin. The linearity of this method was within the concentration range of 10-1000 ng/mL for edaravone in dog plasma. The lower limit of quantification was 10 ng/mL. The relative standard deviations of intra- and inter-precision were <10%. This method was successfully employed in the pharmacokinetics evaluation of edaravone in beagle dogs after intravenous administration.
Formatted abstract
The objective of this study was to investigate the stability of edaravone in dog plasma by using an added antioxidant stabilizer, with an ultimate goal of developing and validating a sensitive, reliable and robust LC–MS-MS method for determination of edaravone in plasma samples. Edaravone was unstable in plasma, but it presented a good stability performance in the plasma with sodium metabisulfite (SMB), an effective antioxidant. The blood sample was collected in the heparinized eppendorf tube containing SMB and plasma sample was deproteinized using acetonitrile containing 20 ng/mL of phenacetin (Internal standard). The chromatographic separation was performed on a Zorbax Extend-C18 analytical column (2.1 mm × 150 mm I.D., particle size 3.5 µm, Agilent Technologies, USA). The mobile phase consisted of 0.1% formic acid in water (v/v) and methanol, and gradient elution was used. The analyte detection was performed on a triple quadrupole tandem mass spectrometer equipped with positive-ion electrospray ionization by multiple reaction ion monitoring mode of the transitions at m/z [M + H]+ 175.1 → 77.1 for edaravone, and m/z [M + H]+ 180.2 → 110.0 for phenacetin. The linearity of this method was within the concentration range of 10–1000 ng/mL for edaravone in dog plasma. The lower limit of quantification was 10 ng/mL. The relative standard deviations of intra- and inter-precision were <10%. This method was successfully employed in the pharmacokinetics evaluation of edaravone in beagle dogs after intravenous administration.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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