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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.\nMethods: 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.\nResults: 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. 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Simple LC-MS/MS Methods for the Quantitation of Total and Free Aprepitant and its Active N-Dealkylated Metabolites in Human Plasma
http://hdl.handle.net/10271/00003895
http://hdl.handle.net/10271/000038953718dc41-47e9-400d-bfa2-1919eb9e8d28
名前 / ファイル | ライセンス | アクション |
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Ther Drug Monit-43-422.pdf (1.5 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||||||||||
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公開日 | 2021-09-22 | |||||||||||||
タイトル | ||||||||||||||
言語 | en | |||||||||||||
タイトル | Simple LC-MS/MS Methods for the Quantitation of Total and Free Aprepitant and its Active N-Dealkylated Metabolites in Human Plasma | |||||||||||||
言語 | ||||||||||||||
言語 | eng | |||||||||||||
キーワード | ||||||||||||||
主題Scheme | Other | |||||||||||||
主題 | aprepitant | |||||||||||||
キーワード | ||||||||||||||
主題Scheme | Other | |||||||||||||
主題 | LC-MS/MS | |||||||||||||
キーワード | ||||||||||||||
主題Scheme | Other | |||||||||||||
主題 | metabolite | |||||||||||||
キーワード | ||||||||||||||
主題Scheme | Other | |||||||||||||
主題 | human plasma | |||||||||||||
キーワード | ||||||||||||||
主題Scheme | Other | |||||||||||||
主題 | free fraction | |||||||||||||
資源タイプ | ||||||||||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||||||||||
資源タイプ | journal article | |||||||||||||
その他のタイトル | ||||||||||||||
その他のタイトル | Quantitation of plasma free aprepitant and its metabolite | |||||||||||||
著者 |
Naito, Takafumi
× Naito, Takafumi
× Suzuki, Yusuke
× Shibata, Kaito
× Kawakami, Junichi
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書誌情報 |
Therapeutic Drug Monitoring 巻 43, 号 3, p. 422-428, 発行日 2021-06 |
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出版者 | ||||||||||||||
出版者 | Wolters Kluwer Health | |||||||||||||
権利 | ||||||||||||||
権利情報 | Copyright 2021 Wolters Kluwer Health. | |||||||||||||
権利 | ||||||||||||||
権利情報 | """This is a non-final version of an article published in final form in """"Therapeutic Drug Monitoring"""", 43(3): p422-428.""" | |||||||||||||
抄録 | ||||||||||||||
内容記述タイプ | Abstract | |||||||||||||
内容記述 | 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. |
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注記 | ||||||||||||||
内容記述タイプ | Other | |||||||||||||
内容記述 | 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 | |||||||||||||
ISSN | ||||||||||||||
収録物識別子タイプ | ISSN | |||||||||||||
収録物識別子 | 0163-4356 | |||||||||||||
EISSN | ||||||||||||||
収録物識別子タイプ | ISSN | |||||||||||||
収録物識別子 | 1536-3694 | |||||||||||||
PubMed番号 | ||||||||||||||
関連タイプ | isVersionOf | |||||||||||||
識別子タイプ | PMID | |||||||||||||
関連識別子 | 32960546 | |||||||||||||
出版社DOI | ||||||||||||||
関連タイプ | isVersionOf | |||||||||||||
識別子タイプ | DOI | |||||||||||||
関連識別子 | 10.1097/FTD.0000000000000815 | |||||||||||||
著者版フラグ | ||||||||||||||
出版タイプ | AM | |||||||||||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa |