Determination and pharmacokinetics and bioavailability of O-demethyl nuciferine in mice by UPLC–MS/MS

Haiya Wu, Mengrou Lu, Jiamin He, Miaoling Huang, Aote Zheng, Meiling Zhang, Congcong Wen, Jufen Ye

Research output: Contribution to journalArticle

Abstract

In this study, a precise, rapid, and accurate ultra-performance liquid chromatography–tandem mass spectrometer (UPLC–MS/MS) method for the quantitation of O-demethyl nuciferine in mouse blood was developed, and pharmacokinetics of O-demethyl nuciferine was studied for the first time after sublingual injection and gavage. The study was performed with an UPLC ethylene bridged hybrid (UPLC BEH) (2.1 mm × 50 mm, 1.7 μm) column at 30 °C, using diazepam as the internal standard (IS). The mobile phase consisted of acetonitrile–10 mmol/L ammonium acetate (containing 0.1% formic acid), with a flow rate of 0.4 mL/min for 4 min run time. Multiple reaction monitoring (MRM) modes of m/z 282.1→219.0 for O-demethyl nuciferine and m/z 296.2→265.1 for IS were utilized to conduct quantitative analysis. Protein in mouse blood was directly precipitated with acetonitrile for sample preparation. The linear range was 1–500 ng/mL with r > 0.995, and the lower limits of quantification (LLOQ) was 1 ng/mL. The intra- and inter-day precision of O-demethyl nuciferine in mouse blood were RSD < 14% and RSD < 15%, respectively.r The accuracy ranged from 89.0% to 110.7%, with a recovery higher than 88.9%, while the matrix effect was between 103.1% and 108.7%. We further applied this UPLC–MS/MS method to the pharmacokinetic study on O-demethyl nuciferine after sublingual injection and gavage and determined the bioavailability to be 6.4%.

Original languageEnglish (US)
Pages (from-to)222-227
Number of pages6
JournalActa Chromatographica
Volume31
Issue number3
DOIs
StatePublished - Jan 1 2019

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Pharmacokinetics
formic acid
Blood
Mass spectrometers
Diazepam
Flow rate
Biological Availability
nuciferine
Recovery
Monitoring
Liquids
Chemical analysis
Proteins

All Science Journal Classification (ASJC) codes

  • Chemistry(all)

Cite this

Wu, Haiya ; Lu, Mengrou ; He, Jiamin ; Huang, Miaoling ; Zheng, Aote ; Zhang, Meiling ; Wen, Congcong ; Ye, Jufen. / Determination and pharmacokinetics and bioavailability of O-demethyl nuciferine in mice by UPLC–MS/MS. In: Acta Chromatographica. 2019 ; Vol. 31, No. 3. pp. 222-227.
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abstract = "In this study, a precise, rapid, and accurate ultra-performance liquid chromatography–tandem mass spectrometer (UPLC–MS/MS) method for the quantitation of O-demethyl nuciferine in mouse blood was developed, and pharmacokinetics of O-demethyl nuciferine was studied for the first time after sublingual injection and gavage. The study was performed with an UPLC ethylene bridged hybrid (UPLC BEH) (2.1 mm × 50 mm, 1.7 μm) column at 30 °C, using diazepam as the internal standard (IS). The mobile phase consisted of acetonitrile–10 mmol/L ammonium acetate (containing 0.1{\%} formic acid), with a flow rate of 0.4 mL/min for 4 min run time. Multiple reaction monitoring (MRM) modes of m/z 282.1→219.0 for O-demethyl nuciferine and m/z 296.2→265.1 for IS were utilized to conduct quantitative analysis. Protein in mouse blood was directly precipitated with acetonitrile for sample preparation. The linear range was 1–500 ng/mL with r > 0.995, and the lower limits of quantification (LLOQ) was 1 ng/mL. The intra- and inter-day precision of O-demethyl nuciferine in mouse blood were RSD < 14{\%} and RSD < 15{\%}, respectively.r The accuracy ranged from 89.0{\%} to 110.7{\%}, with a recovery higher than 88.9{\%}, while the matrix effect was between 103.1{\%} and 108.7{\%}. We further applied this UPLC–MS/MS method to the pharmacokinetic study on O-demethyl nuciferine after sublingual injection and gavage and determined the bioavailability to be 6.4{\%}.",
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Determination and pharmacokinetics and bioavailability of O-demethyl nuciferine in mice by UPLC–MS/MS. / Wu, Haiya; Lu, Mengrou; He, Jiamin; Huang, Miaoling; Zheng, Aote; Zhang, Meiling; Wen, Congcong; Ye, Jufen.

In: Acta Chromatographica, Vol. 31, No. 3, 01.01.2019, p. 222-227.

Research output: Contribution to journalArticle

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