Cyclic phosphatidic acid (cPA), an analog of lysophosphatidic acid, is involved in the regulation of many cellular processes. A sensitive and specific method to quantify the molecular species of cPA is important for studying the physiological and pathophysiological roles of cPA. Here, we developed a liquid chromatography–tandem mass spectrometry (LC–MS/MS)-based quantification method for the simultaneous detection of cPA species having various fatty acids (16:0, 18:0, 18:1, and 18:2) as well as 2-carba-cPA, a chemically synthesized analog of cPA. Chromatography was performed using a reversed-phase C18 column. cPA species were detected using a triple quadrupole mass spectrometer. cPA 17:0 was used as an internal standard. Intra- and interday precision values (CV%) were within 10%. The linear range of detection for each cPA species was 0.01 μg/mL to 5 μg/mL, with correlation coefficients of 0.998 or higher. The developed method was applied to the quantification of cPA species in mouse plasma and organs. The concentrations of cPA 16:0, 18:0, and 18:1 were revealed to be significantly reduced in the brains of cuprizone-treated mice, a model of multiple sclerosis, compared with control mice. These findings could be important for understanding the roles of cPA in the neurodegenerative processes associated with multiple sclerosis.

环状磷脂酸（cPA）是溶血磷脂酸的类似物，参与许多细胞过程的调控。定量分析cPA分子种类的灵敏且特异的方法对于研究cPA的生理和病理生理作用非常重要。在这里，我们开发了一种基于液相色谱-串联质谱（LC-MS / MS）的定量方法，用于同时检测具有多种脂肪酸（16：0、18：0、18：1和18：2）的cPA种类）以及化学合成的cPA类似物2-carba-cPA。使用反相C18柱进行色谱分离。使用三重四极杆质谱仪检测cPA种类。cPA 17：0用作内部标准。日内和日间精度值（CV％）在10％以内。每个cPA种类的线性检测范围是0。01μg/ mL至5μg/ mL，相关系数为0.998或更高。所开发的方法用于定量小鼠血浆和器官中的cPA种类。与对照小鼠相比，铜多唑酮治疗的多发性硬化模型小鼠的大脑中cPA 16：0、18：0和18：1的浓度显着降低。这些发现对于理解cPA在与多发性硬化症相关的神经变性过程中的作用可能很重要。