In this study, a simple and reliable liquid chromatography tandem mass spectrometric method was first developed for the determination of capivasertib in dog plasma with ipatasertib as internal standard. The plasma samples were deproteinated using acetonitrile. An Acquity BEH C₁₈ column (1.7 μm, 2.1 × 50 mm) maintained at 40°C was used for chromatographical separation, with water containing 0.1% formic acid and acetonitrile as mobile phase. Multiple reaction monitoring transitions were m/z 429.2 > 135.1 for capivasertib and m/z 458.2 > 387.2 for ipatasertib, respectively. Excellent linearity was achieved in the concentration range of 1–1,000 ng/ml with a correlation coefficient of >0.9981. The lower limit of quantification was 1 ng/ml. The extraction recovery of capivasertib from dog plasma was >85.81% and no significant matrix effect was found. The intra‐ and inter‐day precision was <9.58% and the accuracy ranged from −10.60% to 12.50%. The validated method was further applied to the pharmacokinetic study of capivasertib in dog plasma after single oral (5 mg/kg) and intravenous (1 mg/kg) administrations. The results revealed that capivasertib was rapidly absorbed into plasma with good bioavailability (47.04%) and low clearance.

中文翻译：

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一种经过验证的LC-MS / MS方法，用于定量狗血浆中capivasertib：在其药代动力学研究中的应用。

在这项研究中，首先开发了一种简单可靠的液相色谱串联质谱法，以ipatasertib作为内标测定狗血浆中的capivasertib。使用乙腈使血浆样品脱蛋白。保持在40°C的Acquity BEH C ₁₈色谱柱（1.7μm，2.1×50 mm）用于色谱分离，流动相为0.1％甲酸和乙腈的水。capivasertib和m / z的多个反应监测转变为m / z 429.2> 135.1ipatasertib分别为458.2> 387.2。在1–1,000 ng / ml的浓度范围内实现了出色的线性，相关系数> 0.9981。定量下限为1 ng / ml。狗血浆中卡帕塞替尼的提取回收率> 85.81％，未发现明显的基质作用。日内和日间精度为<9.58％，精度范围为−10.60％至12.50％。经单次口服（5 mg / kg）和静脉内（1 mg / kg）给药后，已验证的方法可进一步用于卡帕塞替尼在犬血浆中的药代动力学研究。结果显示，capivasertib被快速吸收到血浆中，具有良好的生物利用度（47.04％）和低清除率。