New finding of nalbuphine metabolites in men: NMR spectroscopy and UPLC-MS/MS spectrometry assays in a pilot human study

Hong Jaan Wang, Cheng Huei Hsiong, Li Heng Pao, Wen Liang Chang, Li Jie Zhang, Min Jen Lin, Shung Tai Ho, Pei Wei Huang, Oliver Yoa Pu Hu

研究成果: 雜誌貢獻文章同行評審

13 引文 斯高帕斯(Scopus)

摘要

A safe and efficient semi-synthetic narcotic nalbuphine (NAL) which was broadly applied in analgesic therapy has long been considered to eliminate from human body via phase II conjugation. However, up to the present, neither the complete metabolic pathways nor the identified metabolites of NAL have been clarified in documented reports. In this study, four novel metabolites were discovered by incubating NAL with human liver microsomes. These metabolites were later quantified in blood samples from human volunteers treated with NAL. An accurate and precise new method for simultaneously determining NAL and its metabolites was also established. Their chemical structures were elucidated on the basis of one- and two-dimensional NMR spectroscopic analyses including 1H-1H correlation spectroscopy, nuclear overhauser enhancement spectroscopy, heteronuclear single-quantum correlation, and heteronuclear multiple bond correlation, and further confirmed by mass spectrometry. The analytical method was validated and applied successfully to a pilot human study with ultra-high performance liquid chromatography-tandem mass spectrometry employed with positive ion electrospray ionization via multiple reaction monitoring mode. This is the first report on the qualitative and quantitative analysis of NAL coupled with its two hydroxylated (3′-hydroxynalbuphine and 4′-hydroxynalbuphine) and two conjugated metabolites (nalbuphine-3-β-d-glucuronide and nalbuphine-6-β-d-glucuronide). The present method offers a rapid and simple way of performing pharmacokinetic studies of NAL, and assists in elucidating its metabolic pathway in humans.
原文英語
頁(從 - 到)709-718
頁數10
期刊Metabolomics
10
發行號4
DOIs
出版狀態已發佈 - 1月 1 2014
對外發佈

ASJC Scopus subject areas

  • 生物化學
  • 臨床生物化學
  • 內分泌學、糖尿病和代謝

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