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International Journal of Pharmacology
  Year: 2018 | Volume: 14 | Issue: 2 | Page No.: 215-223
DOI: 10.3923/ijp.2018.215.223
 
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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
Sri Teguh Rahayu, Yahdiana Harahap , Abdul Mun`im and Noorwati Sutandyo

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.
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How to cite this article:

Sri Teguh Rahayu, Yahdiana Harahap, Abdul Mun`im and Noorwati Sutandyo, 2018. 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. International Journal of Pharmacology, 14: 215-223.

DOI: 10.3923/ijp.2018.215.223

URL: https://scialert.net/abstract/?doi=ijp.2018.215.223

 
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