Biological reference materials (RMs) are essential for quality assurance, traceability of measurement results and for method validation. When addressing new measurement questions or emerging regulatory issues, rigorous large-scale CRM production may not be time efficient or economically practical using current production methods. By amending a relatively small matrix batch with a compound(s) of interest at the homogenization step, the National Institute of Standards and Technology (NIST) can create a custom material on an “as-needed” basis and circumvent the time delay inherent in large-batch production, thereby generating a fit-for-purpose, rapid-response RM. Here, Coho salmon (Oncorhynchus kisutch) was cryohomogenized and spiked with an aquaculture antibiotic and antibiotic metabolite. The resultant material was analyzed using liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS) to determine the effectiveness of the amendment technique in a fresh-frozen matrix by assessing homogeneity and accuracy to the target concentration (e.g. mass fraction). Target mass fractions were achieved for both spike components, with RSDs below 5% in replicate measurements of each compound (n = 8). The stability of the spiked compounds was assessed one year post-production and mass fractions were stable, within 1–6% of the initial measurement results, indicating minimal change to the amended analyte concentrations over time. The results support this method as a promising new technique for custom, small-batch RM generation.

生物标准物质 (RM) 对于质量保证、测量结果的可追溯性和方法验证至关重要。在解决新的测量问题或新出现的监管问题时，严格的大规模 CRM 生产可能无法使用当前的生产方法进行时间高效或经济实用。通过在均质化步骤中用感兴趣的化合物修改相对较小的基质批次，美国国家标准与技术研究院 (NIST) 可以“按需”创建定制材料，并规避固有的时间延迟大批量生产，从而生成适合用途、快速响应的 RM。在这里，银大麻哈鱼（Oncorhynchus kisutch）冷冻均质并加入水产养殖抗生素和抗生素代谢物。使用液相色谱-高分辨率串联质谱法 (LC-HRMS/MS) 分析所得材料，通过评估目标浓度（例如质量分数）的均匀性和准确性来确定修正技术在新鲜冷冻基质中的有效性。两种加标组分均达到目标质量分数，每种化合物的重复测量值的 RSD 均低于 5% ( n = 8）。加标化合物的稳定性在生产后一年进行评估，质量分数稳定，在初始测量结果的 1-6% 范围内，表明修正后的分析物浓度随时间变化最小。结果支持这种方法是一种很有前途的定制小批量 RM 生成新技术。