胆囊收缩素（CCK）激素由十二指肠肠内分泌细胞在进食后分泌，并以低皮克摩尔范围循环。目前检测这种消化和食欲调控激素依赖于使用免疫测定法，其中许多法则在生理范围下的敏感性不足以及与胃泌素的交叉反应问题。作为现有技术的替代方法，开发了基于液相色谱和质谱的方法来测量细胞培养上清中的CCK衍生肽。该方法最初应用于器官样研究中，并能够检测到刺激后上清中的CCK8和一个N端肽段（前脂蛋白）ppCCK（21-44）。使用统计建模软件进行了提取优化，实现了对ppCCK（21-44）的定量LC-MS/MS方法，能够检测到低皮克摩尔范围内人体血浆和分泌缓冲液样品中的这种肽。分析了健康个体在隔夜禁食后接受标准餐（Ensure）后的血浆样本；然而，该方法只能检测到ppCCK（21-44）。使用人类肠器官样和健康志愿者的用餐研究证实ppCCK（21-44）是测量体外和体内CCK释放的合适替代分析物。

The hormone cholecystokinin (CCK) is secreted postprandially from duodenal enteroendocrine cells and circulates in the low picomolar range. Detection of this digestion and appetite-regulating hormone currently relies on the use of immunoassays, many of which suffer from insufficient sensitivity in the physiological range and cross-reactivity problems with gastrin, which circulates at higher plasma concentrations. As an alternative to existing techniques, a liquid chromatography and mass spectrometry-based method was developed to measure CCK-derived peptides in cell culture supernatants. The method was initially applied to organoid studies and was capable of detecting both CCK8 and an N-terminal peptide fragment (prepro) ppCCK(21-44) in supernatants following stimulation. Extraction optimization was performed using statistical modeling software, enabling a quantitative LC-MS/MS method for ppCCK(21-44) capable of detecting this peptide in the low pM range in human plasma and secretion buffer solutions. Plasma samples from healthy individuals receiving a standardized meal (Ensure) after an overnight fast were analyzed; however, the method only had sensitivity to detect ppCCK(21-44). Secretion studies employing human intestinal organoids and meal studies in healthy volunteers confirmed that ppCCK(21-44) is a suitable surrogate analyte for measuring the release of CCK in vitro and in vivo.