@article{oai:hama-med.repo.nii.ac.jp:00003769,
 author = {Naito, Takafumi and Suzuki, Yusuke and Shibata, Kaito and Kawakami, Junichi},
 issue = {3},
 journal = {Therapeutic Drug Monitoring},
 month = {Jun},
 note = {雑誌掲載タイトル：Simple Liquid Chromatography?Tandem Mass Spectrometry Method for Quantitation of Total and Free Aprepitant and Its Active N-Dealkylated Metabolites in Human Plasma, Background: Aprepitant, an antiemetic selective neurokinin-1 receptor antagonist, is primarily metabolized to active N-dealkylated form (ND-AP) and then converted to its carbonyl form (ND-CAP) in humans. This study developed simple liquid chromatography-tandem mass spectrometry methods using electrospray ionization (ESI) for the quantitation of plasma total and free aprepitant and its N-dealkylated metabolites and applied it to patient plasma.
Methods: Free aprepitant and ND-AP in plasma were fractionated by centrifugal ultrafiltration. The analytes in plasma or its ultrafiltrated specimen treated by triethylamine/acetonitrile were isocratically separated on a 3-μm octadecylsilyl column with a total run time of 10 minutes and scanned with positive ion ESI.
Results: The calibration curves of total aprepitant, ND-AP, and ND-CAP ranged from 50?2500, 20?1000, and 5?250 ng/mL, respectively, while that of free aprepitant and ND-AP ranged from 2?150 ng/mL. Their intra- and inter-assay accuracy and imprecision values were 93.5 107.7% and 94.6?103.3%, and 2.1?7.5% and 1.0?8.9%, respectively. Aprepitant and its metabolites did not exhibit any matrix effects or instabilities in plasma specimens. In cancer patients receiving oral aprepitant, the plasma concentration ranges of total aprepitant, ND-AP, and ND-CAP, and of free aprepitant and ND-AP were 137?2170, 104?928, 22.4?97.6, 8.11?60.0, and 3.53?56.0 ng/mL, respectively. The median plasma free fraction rates of aprepitant and ND-AP were 4.14% and 4.90%, respectively.
Conclusions: The present methods with acceptable analytical performance can be used to evaluate total and free aprepitant and its N-dealkylated metabolites in patient plasma.},
 pages = {422--428},
 title = {Simple LC-MS/MS Methods for the Quantitation of Total and Free Aprepitant and its Active N-Dealkylated Metabolites in Human Plasma},
 volume = {43},
 year = {2021}
}