A rapid, sensitive, and reliable liquid chromatography‐tandem mass spectrometric method was developed to quantify ipatasertib in dog plasma. The dog plasma sample was deproteinated by using acetonitrile with ulixertinib as an internal standard followed by separation on a Spursil C₁₈‐EP column with a gradient mobile phase comprising 2 mM ammonium acetate containing 0.1% formic acid and acetonitrile. Positive ion electrospray was used, and multiple reaction monitoring transitions were m/z 458.2 > 387.2 for ipatasertib and m/z 433.1 > 262.1 for the internal standard. The developed method was validated with a linear range of 0.3–1500 ng/mL, and with correlation coefficient greater than 0.9989. The lower limit of quantification was 0.3 ng/mL. The intra‐ and inter‐day precision ranged from 3.58 to 14.32%, whereas the intra‐ and inter‐day accuracy was in the range of −2.50–13.25%. No carry‐over and matrix effects were observed under the current conditions. The extraction recovery was demonstrated to be greater than 85.43%. Ipatasertib was stable during the storage, processing, and determination. The validated assay was further successfully applied to a pharmacokinetic study of ipatasertib in dogs after oral and intravenous administrations. The bioavailability of ipatasertib was determined to be 19.3%.

中文翻译：

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使用LC / MS / MS，ipatasertib在犬血浆中的药代动力学和生物利用度。

建立了一种快速，灵敏，可靠的液相色谱-串联质谱法定量狗血浆中的依帕他塞。犬血浆样品通过使用乙腈和ulixertinib作为内标进行脱蛋白，然后在Spursil C ₁₈ -EP色谱柱上进行分离，该色谱柱包含2 mM含0.1％甲酸的乙酸铵和乙腈的梯度流动相。使用正离子电喷雾，ipatasertib和m / z的多个反应监测转换为m / z 458.2> 387.2内标为433.1> 262.1。所开发的方法在0.3–1500 ng / mL的线性范围内验证，相关系数大于0.9989。定量下限为0.3 ng / mL。日内和日间精度在3.58％至14.32％之间，而日间和日间精度在-2.50-13.25％范围内。在当前条件下，未观察到残留和基质效应。萃取回收率证明大于85.43％。伊帕曲替尼在储存，加工和测定过程中稳定。经验证的测定方法进一步成功应用于口服和静脉内给药后ipatasertib在犬体内的药代动力学研究。ipatasertib的生物利用度确定为19.3％。