Absolute oral and subcutaneous bioavailability of ortho-topolin riboside in mice
- Authors
- Won, J.; Oh, S.A.; Shin, H.; Kim, E.; Lee, G.; Noh, K.; Choi, H.-K.; Oh, S.; Kang, W.
- Issue Date
- 30-Nov-2021
- Publisher
- Elsevier B.V.
- Keywords
- HPLC-MS/MS; Mice; Ortho-topolin riboside; Pharmacokinetics
- Citation
- Journal of Pharmaceutical and Biomedical Analysis, v.206
- Journal Title
- Journal of Pharmaceutical and Biomedical Analysis
- Volume
- 206
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/49971
- DOI
- 10.1016/j.jpba.2021.114363
- ISSN
- 0731-7085
1873-264X
- Abstract
- Among essential phytohormones playing a pivotal role in regulating growth and development, ortho-topolin riboside (oTR) exerts the most substantial anti-tumor potency in various cancer cell lines. This study was designed to establish a quantitative determination method for oTR in mouse plasma using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS), to validate the analytical method including stability, and to characterise its pharmacokinetic behaviour in mice. After simple protein precipitation with acetonitrile including kinetin riboside (internal standard), oTR was eluted on a reversed-phase column using a mobile phase of water and acetonitrile (3:7 v/v, including 0.1% formic acid). The protonated precursor ion [M+H]+ and major fragment ion were confirmed at m/z 374.06 and 241.99 for oTR, and 348.23 and 216.06 for the IS, respectively. oTR was stable under bench and storage conditions. The analytical method met the criteria of FDA-validated bioanalytical methods and was successfully applied to a pharmacokinetic study for the first time following oral, subcutaneous, and intravenous administrations. While oTR was merely absorbed by an oral route, 90% of the absolute subcutaneous bioavailability was observed. © 2021 Elsevier B.V.
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