Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.
Medicinal Chemistry and Molecular Modelling Lab, Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.
J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Sep 1;1152:122260. doi: 10.1016/j.jchromb.2020.122260. Epub 2020 Jul 6.
Tamoxifen (TAM) is the choice of a drug approved by the Food and Drug Administration (FDA) for the treatment of estrogen-positive receptor (ER+) breast cancer. Sulphoraphane (SFN), a natural plant antioxidant compound, also acts on estrogen-positive breast cancer receptor. Thus, a combination of TAM with SFN is preferred as it helps to minimize the drug-related toxicity and increases the therapeutic efficacy by providing synergistic anticancer effects of both drugs. In the present study, a new simple, sensitive, precise, and selective UPLC-MS/MS method was developed for the simultaneous quantification of tamoxifen and sulphoraphane using propranolol as an internal standard (IS) in rat plasma. Chromatographic separation was achieved on reverse phase Acquity UPLC BEH C column (50 mm × 2.1 mm, i.d., 1.7 μm) with an isocratic mobile phase composed of solvent A (0.1% formic acid in acetonitrile) and B (0.1% formic acid in water) (80:20, v/v) at a flow-rate of 0.4 mL/min. The detection and quantification of analytes was performed on Waters Zspray Xevo TQD using selected-ion monitoring operated under a positive electrospray ionization mode. The transitions were m/z = 372.0 [M+H] → 71.92 for tamoxifen, m/z = 177.9 [M+H] → 113.9 for sulphoraphane and m/z = 260.3 [M+H] → 116.1 for propranolol. The method was linear over the concentration range of 8-500 ng/mL (r = 0.9996) for tamoxifen, 30-2000 ng/mL (r = 0.9998) for sulphoraphane with insignificant matrix effect and high extraction recovery on spiked quality control (QC) samples. The intra- and inter-batch precisions and accuracy were within the acceptable limits, and both the analytes were found to be stable throughout the short term, long term and freeze thaw stability studies. The validated method was successfully applied for the simultaneous estimation of TAM and SFN in an oral pharmacokinetic study in female Wistar rats. This developed UPLC-MS/MS method could be a valuable tool for future pharmacokinetic interaction, therapeutic drug monitoring and pharmacokinetic characterization of novel formulations.
他莫昔芬（TAM）是美国食品和药物管理局（FDA）批准的用于治疗雌激素阳性受体（ER+）乳腺癌的药物。硫代葡萄糖苷（SFN），一种天然植物抗氧化化合物，也作用于雌激素阳性乳腺癌受体。因此，TAM 与 SFN 的联合使用是首选，因为它有助于最大限度地减少与药物相关的毒性，并通过提供两种药物的协同抗癌作用来提高治疗效果。在本研究中，开发了一种新的简单、灵敏、精确和选择性的 UPLC-MS/MS 方法，用于同时定量测定大鼠血浆中的他莫昔芬和硫代葡萄糖苷，以普萘洛尔为内标（IS）。色谱分离在反相 Acquity UPLC BEH C 柱（50mm×2.1mm，内径，1.7μm）上进行，采用由溶剂 A（乙腈中的 0.1%甲酸）和 B（水中的 0.1%甲酸）（80:20，v/v）组成的等度流动相，流速为 0.4mL/min。使用沃特世 Zspray Xevo TQD 在正电喷雾电离模式下进行选择离子监测进行分析物的检测和定量。跃迁为 m/z=372.0[M+H]→71.92 用于他莫昔芬，m/z=177.9[M+H]→113.9 用于硫代葡萄糖苷，m/z=260.3[M+H]→116.1 用于普萘洛尔。该方法在他莫昔芬的浓度范围为 8-500ng/mL（r=0.9996），硫代葡萄糖苷的浓度范围为 30-2000ng/mL（r=0.9998），具有显著的基质效应和高提取回收率，可用于加标质量控制（QC）样品。日内和日间精密度和准确度均在可接受范围内，两种分析物在短期、长期和冻融稳定性研究中均稳定。经验证的方法成功应用于雌性 Wistar 大鼠口服药代动力学研究中同时测定 TAM 和 SFN。该开发的 UPLC-MS/MS 方法可作为未来药代动力学相互作用、治疗药物监测和新型制剂药代动力学特征的有价值工具。
