Yasu Takeo, Iwatuki Nanami, Gando Yoshito, Matumoto Yasuhiko, Masuo Masahiro, Shirota Mikio, Kobayashi Masayoshi
Department of Medicinal Therapy Research, Education and Research Unit for Comprehensive Clinical Pharmacy, Meiji Pharmaceutical University, Tokyo, Japan.
Bokutoh Hospital-Meiji Pharmaceutical University Joint Research Center, Tokyo, Japan.
Drug Discov Ther. 2024 Sep 19;18(4):260-264. doi: 10.5582/ddt.2024.01049. Epub 2024 Aug 25.
Anamorelin, a non-peptide ghrelin analog and growth hormone secretagogue, is a novel oral drug used to treat cancer cachexia. Patients with cancer cachexia frequently use several drugs and anamorelin is a substrate of cytochrome P450 (CYP) 3A4; therefore, drug-drug interactions with CYP3A4 inhibitors and inducers pose a clinical problem. In this study, we aimed to determine the concentration of anamorelin in human plasma using a simple high-performance liquid chromatography-ultraviolet (HPLC-UV)-based method. The analysis involved extracting a 200-μL plasma sample and protein precipitation using solid-phase extraction. Anamorelin was isocratically separated using a mobile phase consisting of 0.5% potassium dihydrogen phosphate (pH 4.5) and acetonitrile (61:39, v/v) on a Capcell Pack C18 MG II column (250 mm × 4.6 mm) at a flow rate of 1.0 mL/min and monitored at a detection wavelength of 220 nm. The calibration curve was linear within a plasma concentration range of 12.5-1,500 ng/mL, with a coefficient of determination of 0.9999. The intra- and inter-day coefficients of variation were 0.37-6.71% and 2.05-4.77%, respectively. The accuracy of the assay and recovery were 85.25-112.94% and > 86.58%, respectively. This proposed HPLC-UV method is simple and can be applied in clinical settings.
阿那莫林是一种非肽类胃饥饿素类似物和生长激素促分泌素,是一种用于治疗癌症恶病质的新型口服药物。癌症恶病质患者经常使用多种药物,而阿那莫林是细胞色素P450(CYP)3A4的底物;因此,与CYP3A4抑制剂和诱导剂的药物相互作用带来了临床问题。在本研究中,我们旨在使用一种基于高效液相色谱 - 紫外(HPLC - UV)的简单方法测定人血浆中阿那莫林的浓度。分析过程包括提取200μL血浆样品并使用固相萃取进行蛋白沉淀。在Capcell Pack C18 MG II柱(250 mm×4.6 mm)上,以1.0 mL/min的流速,使用由0.5%磷酸二氢钾(pH值4.5)和乙腈(61:39,v/v)组成的流动相进行等度分离阿那莫林,并在220 nm的检测波长下进行监测。校准曲线在12.5 - 1500 ng/mL的血浆浓度范围内呈线性,决定系数为0.9999。日内和日间变异系数分别为0.37 - 6.71%和2.05 - 4.77%。该测定方法的准确度和回收率分别为85.25 - 112.9%和> 86.58%。所提出的HPLC - UV方法简单,可应用于临床环境。