Determination of nootkatone in rat plasma by LC–tandem mass spectrometry and its application in a pharmacokinetic study

This study aimed to develop a rapid, sensitive, and specific LC–tandem mass spectrometry method for the determination of nootkatone in rat plasma. α‐Cyperone was chosen as the internal standard (IS). The plasma was processed using a one‐step acetonitrile protein precipitation method. Chromatographic...

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Bibliographic Details
Published in:Biomedical chromatography 2021-12, Vol.35 (12), p.e5197-n/a
Main Authors: Qin, Zhen‐miao, Li, Yong‐hui, Tan, Yin‐feng, Li, Hai‐long
Format: Article
Language:English
Subjects:
Animals
Chromatography, Liquid - methods
Female
LC–MS/MS
Limit of Detection
Linear Models
method validation
nootkatone
pharmacokinetics
Polycyclic Sesquiterpenes - blood
Polycyclic Sesquiterpenes - chemistry
Polycyclic Sesquiterpenes - pharmacokinetics
Rats
Rats, Sprague-Dawley
Reproducibility of Results
sesquiterpene
Tandem Mass Spectrometry - methods
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Summary:This study aimed to develop a rapid, sensitive, and specific LC–tandem mass spectrometry method for the determination of nootkatone in rat plasma. α‐Cyperone was chosen as the internal standard (IS). The plasma was processed using a one‐step acetonitrile protein precipitation method. Chromatographic separation of nootkatone was achieved on a Phenomenex Kinetex XB‐C18 column (2.10 × 50 mm, 2.6 μm) at 35°C with a mobile phase consisting of acetonitrile and water under a gradient elution at a flow rate of 0.35 mL/min. An electrospray ionization source was applied and operated in positive ion and multiple reaction monitoring modes. Nootkatone and IS were quantified using the transitions of m/z 219.200 → 163.110 and m/z 219.200 → 111.000, respectively. The calibration curves were linear over the range of 10–2000 ng/mL (r = 0.9943). The lower limit of quantification was 10 ng/mL. The intra‐ and inter‐day precision (relative standard deviation) ranged from 2.56% to 8.41%, with the accuracy values ranging from 98.9% to 99.17% for four different concentration levels. The matrix effect and extraction recovery were within acceptable limits. The validated method was successfully applied to the pharmacokinetic study of nootkatone in rats after oral and intravenous administration at three dosages. The main pharmacokinetic parameters were calculated, showing low bioavailability of nootkatone.
ISSN:0269-3879
1099-0801
DOI:10.1002/bmc.5197