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

作者：Rahayu Sri Teguh; Harahap Yahdiana^*; Mun'im Abdul; Sutandyo Noorwati

来源：International Journal of Pharmacology, 2018, 14(2): 215-223.

DOI：10.3923/ijp.2018.215.223

• Tamoxifen
• 4-OHTAM
• Myrmecodia erinaceae Becc.
• Rat plasma
• anti-oestrogen

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 (R) column (100 mm X2.1 mm x 1.7 mu m) and a column temperature of 40 degrees 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.

• 出版日期2018