Determination of tamoxifen and 4-hydroxytamoxifen levels in rat plasma after administration of the ethyl acetate fraction of myrmecodia erinaceae Becc. Using liquid chromatography tandem mass-spectrometry

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Abstract

Background and Objective: The effects of anti-oestrogen and the side effects of tamoxifen and its metabolite 4-Hydroxytamoxifen (4-OHTAM) depend on their levels in plasma. The ethyl acetate fraction of Myrmecodia erinaceae Becc. was observed to effect the plasma levels of tamoxifen and 4-OHTAM. A sensitive, selective and valid method is needed to quantitatively determine the concentration of tamoxifen and 4-OHTAM in plasma. Methodology: Tamoxifen and 4-OHTAM were simultaneously extracted from plasma by protein precipitation using acetonitrile-0.2% formic acid. It was then analyzed using liquid chromatography tandem mass-spectrometry (LC-MS/MS) with a C18 ACQUITY® column (100 mm×2.1 mm x 1.7 µm) and a column temperature of 40°C. The mobile phase consisted of acetonitrile-0.2% formic acid, 0.2% formic acid (70:30 v/v) and a flow rate of 0.2 mL min-1. A total of 30 female white rats (Sprague-Dawley) were divided into 6 groups (KKN, KP, KN, D100, D200 and D400). With the exception of the KKN group, all the groups were given tamoxifen 20 mg kg-1 b.wt. Then, 30 min later the D100, D200 and D400 groups were given an ethyl acetate fraction equivalent to quercetin 100, 200 and 400 mg kg-1 b.wt., respectively, once a day for 20 days. Blood was collected and analyzed every day. Results: The analytical method was linear (r>0.99) in the range concentration of 2-200 ng mL-1 for tamoxifen and 4-OHTAM. All the validation parameters met the criteria of the 2011 European Medicines Agency (EMA) guidelines. The concentrations of tamoxifen and 4-OHTAM decreased after administration of the ethyl acetate fraction for 20 days and tamoxifen metabolism was inhibited. Conclusion: The proposed method simultaneously measured the concentrations of tamoxifen and 4-OHTAM in plasma in female rats.

Original languageEnglish
Pages (from-to)215-223
Number of pages9
JournalInternational Journal of Pharmacology
Volume14
Issue number2
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • 4-OHTAM
  • Anti-oestrogen
  • Myrmecodia erinaceae Becc
  • Rat plasma
  • Tamoxifen

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