Plasma free metanephrines are widely used for the diagnosis of pheochromocytoma and paraganglioma (PPGL), yet quantifying metanephrines using a simple and cost-effective approach may be challenging due to preanalytical and analytical constraints. In this study, we established and validated a new method for quantitative measurement of plasma free metanephrines based on microextraction by packed sorbent (MEPS) with porous graphitic carbon (PGC) and liquid chromatography-tandem mass spectrometry (HILIC-MS/MS). The elution step was fully compatible with HILIC mode without evaporation and reconstitution. The analytes were well resolved, and potential interferences (54 substances) were investigated. This method was linear from 24.7–2717 pg/mL for metanephrine (MN) and 24.5–4010 pg/mL for normetanephrine (NMN) with a coefficient of determination (R²) higher than 0.994. The limit of MN and NMN detection were 12.4 pg/mL and 12.3 pg/mL, respectively. The intra- and interassay impressions were ≤12.8% for spiked quality controls and ≤13.6% for commercial quality controls; the method recoveries ranged within 88.0–109.0%, respectively. The area under the receiver operating characteristic (ROC) curve was 0.848 ± 0.047 for MN and 0.979 ± 0.021 for NMN. Validation that was performed by comparing clinical specimens with various biochemical results showed that plasma free metanephrines in a seated position had comparable sensitivity and lower specificity to urinary free metanephrines, which could be compensated by combining other biochemical tests. The newly developed MEPS method resulted as a time-saving, reliable, and cost-effective microextraction technique that can be applied for a successful screening of PPGL.

中文翻译：

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用多孔石墨碳和液相色谱-串联质谱法简单，经济高效的微萃取填充吸附剂定量测定血浆中无肾上腺素

无血浆肾上腺素被广泛用于嗜铬细胞瘤和副神经节瘤（PPGL）的诊断，但是由于分析和分析的限制，采用简单且经济高效的方法定量甲肾上腺素可能会面临挑战。在这项研究中，我们建立和验证了一种新的定量测定血浆游离甲基肾上腺素的新方法，该方法基于多孔石墨碳（PGC）和液相色谱-串联质谱（HILIC-MS / MS）的填充吸附剂（MEPS）微萃取。洗脱步骤与HILIC模式完全兼容，无需蒸发和重建。分析物的分离度很好，并研究了潜在的干扰（54种物质）。对于偏肾上腺素（MN），此方法线性为24.7–2717 pg / mL，对于正甲肾上腺素（NMN），此方法为24.5–4010 pg / mL，测定系数为（R ²）高于0.994。MN和NMN的检出限分别为12.4 pg / mL和12.3 pg / mL。掺入质量控制的批内和批间印象≤12.8％，商业质量控制的批内印象为≤13.6％；该方法的回收率分别在88.0–109.0％之间。MN的接收器工作特性（ROC）曲线下的面积为0.848±0.047，NMN的接收器工作特性（ROC）曲线下的面积为0.979±0.021。通过比较临床标本和各种生化结果进行的验证显示，就坐位置的无血浆肾上腺素与尿中游离肾上腺素具有相当的敏感性和较低的特异性，这可以通过结合其他生化试验来弥补。新开发的MEPS方法可节省时间，可靠，