Diospyros kaki fruits possess great beneficial properties for human health due to their strong antioxidant and antiradical activities related to the high level of bioactive compounds and particularly polyphenols. In this paper a rapid and efficient liquid chromatography–tandem mass spectrometry method for the determination of 38 polyphenolic compounds in Diospyros kaki flesh was developed. The optimization of the chromatographic method was performed applying a Quality by Design approach, which is unexplored in the field of food analysis. The Critical Method Attributes (CMAs) were the critical resolutions of some isobaric compounds and analysis time. The Critical Methods Parameters (CMPs) were related to the characteristics of both the mobile phase and the column: flow rate, temperature, starting organic phase concentration of the mobile phase, formic acid percentage in the eluents, type of organic solvent in the mobile phase and gradient of organic eluents. The effects of the CMPs on the CMAs were evaluated by experimental design, at first carrying out a screening phase by an asymmetric screening matrix and then applying Response Surface Methodology by a Doehlert Design. The quadratic polynomial models postulated to link the CMAs to CMPs were calculated and the Method Operable Design Region was identified with the aid of Monte Carlo simulations as the multidimensional combination of the CMPs that satisfied the requirements for the CMAs with a probability ≥90%. The developed method was applied to real samples obtained by the extraction of Diospyros kaki flesh from two different cultivars (Rojo Brillante and Kaki Tipo), making it possible to obtain extensive information on their polyphenolic profiles.

柿柿果因其强大的抗氧化剂和抗自由基活性与高水平的生物活性化合物（尤其是多酚）有关，因此对人体健康具有极大的益处。本文采用快速高效的液相色谱-串联质谱法测定柿柿中的38种多酚类化合物肉发达。色谱方法的优化是通过“设计质量”方法进行的，这在食品分析领域尚待探索。关键方法属性（CMA）是某些同量异位化合物的关键分辨率和分析时间。关键方法参数（CMP）与流动相和色谱柱的特征有关：流速，温度，流动相的起始有机相浓度，洗脱液中的甲酸百分比，流动相中有机溶剂的类型和有机洗脱液的梯度。通过实验设计评估了CMP对CMA的影响，首先通过非对称筛选矩阵进行筛选阶段，然后通过Doehlert Design应用响应表面方法。计算了假定将CMA连接到CMP的二次多项式模型，并借助Monte Carlo模拟确定了方法可操作设计区域为CMP的多维组合，其满足CMA要求的概率≥90％。所开发的方法被应用于通过萃取提取的真实样品中。来自两个不同品种（Rojo Brillante和Kaki Tipo）的Diospyros柿果肉，使得有可能获得有关其多酚谱的大量信息。