Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Ahmedabad, Gujarat, India.
Biomed Chromatogr. 2020 Jun;34(6):e4825. doi: 10.1002/bmc.4825. Epub 2020 Mar 31.
Treatment through a combination of drugs involving cyclin D-dependent kinase inhibitors like abemaciclib and aromatase inhibitor like letrozole proved to be a potential therapeutic regimen and first-line treatment in estrogen receptor-positive breast cancer. In this study, we developed a simple and simultaneous RP-HPLC bioanalytical method for quantifying abemaciclib and letrozole in rat plasma. Abemaciclib and letrozole were separated on Zorbax Eclipse C column employing a gradient elution method comprising 10 mM ammonium acetate (pH 5) and acetonitrile as mobile phase. The method was found to have acceptable selectivity, accuracy (97.20-118.17%), precision (1.10-9.39%) and stability in the validation experiment performed as per the US Food and Drug Administration guidelines. The method sensitivity was low at a concentration level of 100 ng/ml. The applicability of the method has been verified through a single-dose oral pharmacokinetic study in rat. The developed method will be useful to quantitate the analytes in rat plasma samples of different preclinical studies including their pharmacokinetic drug-drug interactions in the future. To date, no method has been reported for the quantification of abemaciclib and letrozole simultaneously in any type of biological matrices. Therefore, this study makes a definite significant contribution in the field of bioanalytical research.
通过联合使用涉及细胞周期蛋白依赖性激酶抑制剂（如阿贝西利）和芳香酶抑制剂（如来曲唑）的药物治疗，已被证明是一种有潜力的治疗方案，也是雌激素受体阳性乳腺癌的一线治疗方法。在这项研究中，我们开发了一种简单且同时的反相高效液相色谱生物分析方法，用于定量检测大鼠血浆中的阿贝西利和来曲唑。阿贝西利和来曲唑在 Zorbax Eclipse C 柱上采用梯度洗脱法分离，流动相由 10 mM 乙酸铵（pH 5）和乙腈组成。该方法在按照美国食品和药物管理局指南进行的验证实验中表现出可接受的选择性、准确性（97.20-118.17%）、精密度（1.10-9.39%）和稳定性。该方法的灵敏度在 100ng/ml 的浓度水平较低。通过在大鼠中进行单次口服药代动力学研究验证了该方法的适用性。该方法将有助于在未来的不同临床前研究中定量分析大鼠血浆样本中的分析物，包括它们的药代动力学药物相互作用。迄今为止，尚未有任何方法在任何类型的生物基质中同时定量测定阿贝西利和来曲唑。因此，这项研究在生物分析研究领域做出了明确的重要贡献。
