Development of LC‐MS/MS determination method and backpropagation artificial neural networks pharmacokinetic model of febuxostat in healthy subjects.

What is known and objective: Febuxostat is a well‐known drug for treating hyperuricemia and gout. The published methods for determination of febuxostat in human plasma might be unsuitable for high‐throughput determination and widespread application. We need to develop a highly selective, sensitive a...

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Publicado en:Journal of Clinical Pharmacy & Therapeutics Vol. 46; no. 2; pp. 333 - 343
Autores principales: Xu, Yichao, Chen, Jinliang, Yang, Dandan, Hu, Yin, Hu, Xinhua, Jiang, Bo, Ruan, Zourong, Lou, Honggang
Formato: pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell Apr2021
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Apr2021
      vid: 46
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1111/jcpt.13285
        149308336
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        atl: Development of LC‐MS/MS determination method and backpropagation artificial neural networks pharmacokinetic model of febuxostat in healthy subjects.
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        au:
          Xu, Yichao
          Chen, Jinliang
          Yang, Dandan
          Hu, Yin
          Hu, Xinhua
          Jiang, Bo
          Ruan, Zourong
          Lou, Honggang
        affil: Center of Clinical Pharmacology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou Zhejiang, , China
      sug:
        subj:
          Chromatography, Liquid Methods
          Mass Spectrometry Methods
          Neural Networks (Computer)
          Thiazoles Pharmacokinetics
          Hyperuricemia Drug Therapy
          Gout Drug Therapy
          Thiazoles Blood
          Molecular Structure
          Human
          Acids, Acyclic
          Organic Chemicals
          Chromatography
          Descriptive Statistics
          Drug Monitoring
      ab: What is known and objective: Febuxostat is a well‐known drug for treating hyperuricemia and gout. The published methods for determination of febuxostat in human plasma might be unsuitable for high‐throughput determination and widespread application. We need to develop a highly selective, sensitive and rapid liquid chromatography‐tandem mass spectrometry method. Methods: The chromatographic separation was achieved on a Hypersil Gold‐C18 (2.1 mm × 100 mm, 1.9 μm) column with mobile phase A (Water containing 0.1% formic acid) and mobile phase B (acetonitrile containing 0.1% formic acid). Multiple reaction monitoring (MRM) mode was used for quantification using target ions at m/z 315.3 → m/z 271.3 for febuxostat and m/z 324.3 → m/z 280.3 for Febuxostat‐d9 (IS). A backpropagation artificial neural network (BPANN) pharmacokinetic model was constructed by the data of bioequivalence study. Results and Discussion: After the LC‐MS/MS method validated, it was successfully applied to the bioequivalence study of 30 human volunteers under fed condition. The predicted concentrations generated by BPANN model had a high correlation coefficient with experimental values. What is new and conclusion: A sensitive LC‐MS/MS method had been developed and validated for determination of febuxostat in healthy subjects under fed condition, and a BPANN model was developed that can be used to predict the plasma concentration of febuxostat.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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