Sensitive analysis of very low‐molecular weight metabolites using liquid chromatography with quadrupole‐time‐of‐flight mass spectrometry is challenging due to the high losses of ions in a time‐of‐flight analyzer. Improvement in sensitivity for these analytes via the optimization of advanced parameters, including quadrupole profile, ion guide parameters, and duty cycle, has been achieved. The optimization of the method was carried out using a large spectrum of structurally different compounds including (iso)flavonoids and their known metabolites. These compounds can be categorized into two major groups, that is, compounds with (iso)flavonoid core and low‐molecular weight phenolics. The optimization of the duty cycle enabled up to a 15‐fold increase in analyte responses while the contribution of tuning ion optics and quadrupole profile was negligible. The limits of quantifications of our new method were assessed using both standard solutions and rat plasma. They were decreased at least 10 times for several low‐molecular weight phenolics enabling measurement of their concentrations in a range of 1‐50 ng/mL in rat plasma after protein precipitation. Concurrently, the limits of quantifications for compounds with (iso)flavonoid core did not increase distinctly allowing their detection in a range of 0.5‐10 ng/mL. The new method was used for the targeting of phenolics in biological samples from pharmacokinetics experiments.

中文翻译：

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具有超高灵敏度的高分辨率 LC-MS 分析大鼠血浆中的酚类物质

由于飞行时间分析仪中离子的高损失，使用液相色谱和四极杆飞行时间质谱法对极低分子量代谢物进行灵敏分析具有挑战性。通过优化高级参数（包括四极杆轮廓、离子导向器参数和占空比），已经实现了对这些分析物的灵敏度的提高。该方法的优化是使用大量结构不同的化合物进行的，包括（异）类黄酮及其已知代谢物。这些化合物可分为两大类，即具有（异）类黄酮核心的化合物和低分子量酚类化合物。占空比的优化使分析物响应增加了 15 倍，而调谐离子光学和四极杆轮廓的贡献可以忽略不计。使用标准溶液和大鼠血浆评估了我们新方法的定量限。对于几种低分子量酚类物质，它们至少减少了 10 倍，从而能够在蛋白质沉淀后测量大鼠血浆中 1-50 ng/mL 的浓度。同时，具有（异）类黄酮核心的化合物的定量限没有明显增加，允许在 0.5-10 ng/mL 的范围内进行检测。新方法用于靶向药代动力学实验中生物样品中的酚类物质。对于几种低分子量酚类物质，它们至少减少了 10 倍，从而能够在蛋白质沉淀后测量大鼠血浆中 1-50 ng/mL 的浓度。同时，具有（异）类黄酮核心的化合物的定量限没有明显增加，允许在 0.5-10 ng/mL 的范围内进行检测。新方法用于靶向药代动力学实验中生物样品中的酚类物质。对于几种低分子量酚类物质，它们至少减少了 10 倍，从而能够在蛋白质沉淀后测量大鼠血浆中 1-50 ng/mL 的浓度。同时，具有（异）类黄酮核心的化合物的定量限没有明显增加，允许在 0.5-10 ng/mL 的范围内进行检测。新方法用于靶向药代动力学实验中生物样品中的酚类物质。