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An HPLC-MS/MS Method for Pharmacokinetic Study of Y-99: A Novel Diuretic Agent Targeting Urea Transporters.
Journal of Chromatographic Science ( IF 1.5 ) Pub Date : 2023-07-09 , DOI: 10.1093/chromsci/bmac089
Yue Xu 1 , Shuyuan Wang 1 , Wen Ma 2 , Jun Li 2 , Yingyuan Lu 2 , Abudumijiti Abulizi 1 , Jianguo Sun 3 , Baoxue Yang 1
Affiliation  

Y-99, a promising first-in-class diuretic, is a novel urea transporter inhibitor with oral diuretic activity. However, little is known about the pharmacokinetic profiles of Y-99 in experimental animals. In this study, a method of quantitative determination of Y-99 in rat plasma based on high-performance liquid chromatography-tandem mass spectrometry was developed and validated in selectivity, linearity, recovery and matrix effect, accuracy and precision, stability, carry-over and dilution integrity. Chromatographic separation was conducted on an ACQUITY BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with gradient elution at a 0.3 mL/min flow rate after protein precipitation. Mass spectrometry was performed by a positive electrospray ionization mass spectrometer in multiple reaction monitoring mode. The method showed standard-compliant linearity (1-1,000 ng/mL, r = 0.9991). The intra-day and inter-day accuracy (relative error < 11.2%) and precision (coefficient of variation <8.4%) were within acceptable criteria. The recovery and matrix effects were 97.3-110.7% and 103.7-107.5%, respectively. The stability, dilution integrity and carry-over of the method were also within the acceptable criteria. Pharmacokinetic profiles of Y-99 in rats were first investigated using this method, which was vital for developing novel diuretics without electrolyte imbalance targeting urea transporters.

中文翻译:


Y-99 药代动力学研究的 HPLC-MS/MS 方法:一种针对尿素转运蛋白的新型利尿剂。



Y-99是一种有前途的一流利尿剂,是一种具有口服利尿活性的新型尿素转运蛋白抑制剂。然而,对于 Y-99 在实验动物中的药代动力学特征知之甚少。本研究建立了一种基于高效液相色谱-串联质谱法的大鼠血浆中Y-99的定量测定方法,并在选择性、线性、回收率和基质效应、准确度和精密度、稳定性、残留等方面进行了验证。和稀释完整性。蛋白质沉淀后,在 ACQUITY BEH C18 柱(2.1 mm × 50 mm,1.7 μm)上进行色谱分离,以 0.3 mL/min 流速进行梯度洗脱。质谱分析是通过正电喷雾电离质谱仪以多反应监测模式进行的。该方法显示出符合标准的线性(1-1,000 ng/mL,r = 0.9991)。日内和日间准确度(相对误差<11.2%)和精密度(变异系数<8.4%)均在可接受的标准范围内。回收率和基质效应分别为97.3-110.7%和103.7-107.5%。该方法的稳定性、稀释完整性和残留也在可接受的标准范围内。首先使用该方法研究了 Y-99 在大鼠中的药代动力学特征,这对于开发针对尿素转运蛋白的新型无电解质失衡的利尿剂至关重要。
更新日期:2022-11-11
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