The scientific impact of translational biomedical research largely depends on the availability of high-quality biomaterials. However, evidence-based and robust quality indicators (QIs) covering the most relevant preanalytical variations are still lacking. The aim of this study was to identify and validate a QI suitable for assessing time-to-centrifugation (TTC) delays in human liquid biospecimens originating from both healthy and diseased individuals. Serum and plasma samples with varying TTCs were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in a pilot cohort of healthy individuals to identify a suitable QI candidate. Taurine (TAU), as a TTC QI candidate, was validated in healthy individuals and patients with rheumatologic and cardiologic diseases, considering the (1) preanalytical handling temperature, (2) platelet count, and (3) postcentrifugation delay. For discrimination of high TTC (TTC >60 minutes) from low TTC serum specimens, a probability calculation tool was developed (Triple-T-cutoff-model). TTC-dependent changes in healthy individuals were observed for amino acids, particularly TAU. Validation of the TAU levels in an independent cohort of healthy individuals revealed a time-dependent increase in serum, but not in plasma, for a TTC delay of 30-240 minutes. TAU increases were dependent on the handling temperature and platelet count and volume. By contrast, no changes in TAU concentrations were observed for additional postcentrifugation delays. Validation of TAU and the Triple-T-cutoff-model, in rheumatologic/cardiologic patient collectives, allowed the discrimination of samples with TTC ≤60 min/>60 min with estimated AUROC (area under the receiver operating characteristic curve) values of 89% [78%-100%]/86% [71%-100%] and 91% [79%-100%]/84% [68%-100%], respectively. Considering the preanalytical handling temperature and platelet count and volume, TAU and the Triple-T-cutoff-model represent reliable QIs for TTC >60 minutes in serum samples from healthy individuals and selected rheumatologic/cardiologic patients. However, further studies in larger patient collectives with various diseases are needed to assess the robustness and potential of the QIs presented in this article as biobanking quality assurance/quality control tools to support high-quality biomedical research.

中文翻译：

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液体生物库中分析前工作流程的质量评估：牛磺酸作为分析前过程变化的血清特异性质量指标。

转化生物医学研究的科学影响在很大程度上取决于高质量生物材料的可用性。但是，仍然缺乏涵盖最相关的分析前变化的基于证据的可靠质量指标（QIs）。这项研究的目的是鉴定和验证一种适合评估源自健康和患病个体的人类液体生物标本中的离心时间（TTC）延迟的QI。在健康个体的试验队列中，通过液相色谱-串联质谱（LC-MS / MS）分析具有不同TTC的血清和血浆样品，以确定合适的QI候选者。考虑到（1）分析前的处理温度，牛磺酸（TAU）作为TTC QI候选药物已在健康个体和风湿性心脏病患者中得到验证。（2）血小板计数，和（3）离心后延迟。为了区分低TTC血清标本中的高TTC（TTC> 60分钟），开发了一种概率计算工具（三重T截止模型）。观察到健康个体中TTC依赖性的氨基酸变化，尤其是TAU。在一个独立的健康个体队列中，对TAU水平的验证显示，TTC延迟30-240分钟，血清而不是血浆随时间增加。TAU的增加取决于处理温度以及血小板计数和体积。相反，对于额外的离心后延迟，未观察到TAU浓度的变化。在风湿病/心脏病患者集体中验证TAU和三重T截止模型可以区分TTC≤60 min的样品 60分钟，估计的AUROC（接收器工作特性曲线下的面积）值为89％[78％-100％] / 86％[71％-100％]和91％[79％-100％] / 84％[68 ％-100％]。考虑到分析前的处理温度，血小板数量和体积，TAU和Triple-T-cutoff模型代表健康个体和某些风湿病/心脏病患者血清样品中TTC> 60分钟的可靠QI。但是，需要在具有各种疾病的更大患者群体中进行进一步研究，以评估本文中作为生物银行质量保证/质量控制工具以支持高质量生物医学研究的QI的鲁棒性和潜力。考虑到分析前的处理温度，血小板数量和体积，TAU和Triple-T-cutoff模型代表健康个体和某些风湿病/心脏病患者血清样品中TTC> 60分钟的可靠QI。但是，需要在具有各种疾病的更大患者群体中进行进一步研究，以评估本文中作为生物银行质量保证/质量控制工具以支持高质量生物医学研究的QI的鲁棒性和潜力。考虑到分析前的处理温度，血小板数量和体积，TAU和Triple-T-cutoff模型代表健康个体和某些风湿病/心脏病患者血清样品中TTC> 60分钟的可靠QI。但是，需要在具有各种疾病的更大患者群体中进行进一步研究，以评估本文中作为生物银行质量保证/质量控制工具以支持高质量生物医学研究的QI的鲁棒性和潜力。