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Abstract：
A sensitive and selective LC-MS/MS method was developed and validated for the quantitation of a novel Gαi2 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.
摘要：
开发了一种灵敏和选择性的LC-MS/MS方法，并对其进行了验证，用于定量新型Gαi2抑制剂，GT-14，在大鼠血浆中使用配备有ExionLCUHPLC单元的SCIEX6500+三重QUADLC-MS系统。GT-14(m/z265.2→134.1)和灰黄霉素(内标，IS）（m/z353.1→285.1）通过电喷雾电离（ESI）使用多反应监测（MRM）以阳性模式检测。该测定在大鼠血浆中0.78-1000ng/mL的浓度范围内呈线性关系。准确度和精密度值均在±15%的验收标准内，根据FDA的指导。基质效应从等离子体中可以忽略不计，信号百分比为98.5-106.9%。平均回收率为104.5%，表明从血浆中完全提取了GT-14。发现GT-14在不同的实验条件下是稳定的。验证的方法已成功用于评估大鼠血浆蛋白结合和GT-14的体内药代动力学。
