开发并验证了一种新型 Gα2 抑制剂 GT-14 的灵敏 LC-MS/MS 检测方法，用于大鼠血浆中的测定，并将其应用于药代动力学研究。
Development and validation of a sensitive LC-MS/MS assay of GT-14, a novel Gα2 inhibitor, in rat plasma, and its application in pharmacokinetic study.
机构信息
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA.
School of Chemistry and Biochemistry, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA 30318, USA.
出版信息
J Pharm Biomed Anal. 2024 Aug 1;245:116183. doi: 10.1016/j.jpba.2024.116183. Epub 2024 May 3.
A sensitive and selective LC-MS/MS method was developed and validated for the quantitation of a novel Gα2 inhibitor, GT-14, in rat plasma using a SCIEX 6500+ triple QUAD LC-MS system equipped with an ExionLC UHPLC unit. GT-14 (m/z 265.2 → 134.1) and griseofulvin (Internal Standard, IS) (m/z 353.1 → 285.1) were detected in a positive mode by electrospray ionization (ESI) using multiple reaction monitoring (MRM). The assay was linear in the concentration range of 0.78-1000 ng/mL in rat plasma. Both accuracy and precision values were within the acceptance criteria of ±15 %, as established by FDA guidance. The matrix effect was negligible from plasma, with signal percentages of 98.5-106.9 %. The mean recovery was 104.5 %, indicating complete extraction of GT-14 from plasma. GT-14 was found to be stable under different experimental conditions. The validated method was successfully applied to evaluate plasma protein binding and in vivo pharmacokinetics of GT-14 in rats.
建立并验证了一种灵敏、专属性的 LC-MS/MS 方法，用于大鼠血浆中新型 Gα2 抑制剂 GT-14 的定量分析，该方法采用 SCIEX 6500+ 三重四极杆 LC-MS 系统，配备 ExionLC UHPLC 单元。GT-14（m/z 265.2→134.1）和灰黄霉素（内标，IS）（m/z 353.1→285.1）采用电喷雾电离（ESI）在正离子模式下，通过多重反应监测（MRM）进行检测。在大鼠血浆中，该测定法的浓度范围为 0.78-1000ng/mL 时呈线性。如 FDA 指南所规定，准确度和精密度值均在 ±15%的可接受标准范围内。从血浆中得到的基质效应可以忽略不计，信号百分比为 98.5-106.9%。平均回收率为 104.5%，表明 GT-14 可从血浆中完全提取。在不同的实验条件下，GT-14 均稳定。该验证方法成功地应用于评估 GT-14 在大鼠中的血浆蛋白结合和体内药代动力学。
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