Determination of Penicillium griseofulvum-oriented pyripyropene A, a selective inhibitor of acyl-coenzyme A: cholesterol acyltransferase 2, in mouse plasma using liquid chromatography-tandem mass spectrometry and its application to pharmacokinetic studies

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Title
Determination of Penicillium griseofulvum-oriented pyripyropene A, a selective inhibitor of acyl-coenzyme A: cholesterol acyltransferase 2, in mouse plasma using liquid chromatography-tandem mass spectrometry and its application to pharmacokinetic studies
Author(s)
Kyeong-Ryoon Lee; Song Hee Chae; Min Ju Kim; Y J Chae; Myung Yeol LeeChang Woo LeeJong Soon KangWoon Kee YoonYoung Suk WonKihoon LeeOg Sung Moon; Young-Kook Kim; Hyoung-Chin Kim
Bibliographic Citation
Biomedical Chromatography, vol. 33, no. 2, pp. e4388-e4388
Publication Year
2019
Abstract
In this study, we developed a method for the determination of Penicillium griseofulvum-oriented pyripyropene A (PPPA), a selective inhibitor of acyl-coenzyme A:cholesterol acyltransferase 2, in mouse and human plasma and validated it using liquid chromatography-tandem mass spectrometry. Pyripyropene A (PPPA) and an internal standard, carbamazepine, were separated using a Xterra MS C18 column with a mixture of acetonitrile and 0.1% formic acid as the mobile phase. The ion transitions monitored in positive-ion mode [M?+?H]+ of multiple-reaction monitoring (MRM) were m/z 148.0 from m/z 584.0 for PPPA and m/z 194.0 from m/z 237.0 for the internal standard. The detector response was specific and linear for PPPA at concentrations within the range from 1 to 5,000?ng/mL. The intra-/inter-day precision and accuracy of the method was acceptable by the criteria for assay validation. The matrix effects of PPPA ranged from 97.6 to 104.2% and from 93.3 to 105.3% in post-preparative mouse and human plasma samples, respectively. PPPA was also stable under various processing and/or handling conditions. Finally, PPPA concentrations in the mouse plasma samples could be measured after intravenous, intraperitoneal, or oral administration of PPPA, suggesting that the assay is useful for pharmacokinetic studies on mice and applicable to human studies.
Keyword
ACAT2LC-MS/MSPyripyropene Amethod validationpharmacokinetics
ISSN
0269-3879
Publisher
Wiley
DOI
http://dx.doi.org/10.1002/bmc.4388
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
Ochang Branch Institute > Division of Bioinfrastructure > 1. Journal Articles
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