The determination of individual prostaglandins (PG) in humans is mainly performed in urine samples. The quantification of PGs in human plasma could improve the understanding of particular PG species under various physiological and pathological conditions. 15-Deoxy-Δ^12,14-prostaglandin J₂ (15d-PGJ₂) is a dehydrated downstream product of PGD₂ and is of high interest due to its recently discovered anti-inflammatory effects. Increasing availability of highly sensitive mass spectrometry allows the quantification of low abundant biomarkers like 15d-PGJ₂ in human plasma samples. Herein, a sensitive LC-MS/MS method for the determination of 15d-PGJ₂ was established. The method was validated according to the guidance of the American Food and Drug Administration and tested in plasma samples from patients with poorly controlled diabetes, considered to be a pro-inflammatory condition. Extraction of 15d-PGJ₂ was achieved with an easy-to-use liquid-liquid extraction by ethyl acetate following a methanol precipitation. The lower limit of quantification was 2.5 pg mL⁻¹ and linearity (R² = 0.998) was guaranteed between 2.5 and 500 pg mL⁻¹ for 15d-PGJ₂. Selectivity was assured by the use of two individual mass transitions (qualifier and quantifier). Precision and accuracy were validated in an inter- and intraday assay with a coefficient of variation below 11.8% (intraday) and 14.7% (interday). In diabetic patients with an HbA_1C > 9%, increased plasma concentrations of 15d-PGJ₂ compared to control plasma were measured. 15d-PGJ₂ correlated negatively with the inflammation marker C-reactive protein. The developed LC-MS/MS method represents a new possibility to quantify 15d-PGJ₂ with high specificity in human plasma samples. This may contribute to a better understanding of the potential anti-inflammatory effects of 15d-PGJ₂ in severe long-term pro-inflammatory disorders like diabetes, cancer, or cardiovascular disease.

中文翻译：

---

灵敏质谱测定15-脱氧-Δ12,14-前列腺素J 2及其在糖尿病患者血浆中的应用

人类中单个前列腺素（PG）的测定主要在尿液样品中进行。人血浆中PG的定量可以提高人们在各种生理和病理条件下对特定PG种类的了解。15-去氧Δ ^12,14 -前列腺素Ĵ ₂（15D-PGJ ₂）是PGD的脱水下游产品的₂和是高息的，由于其最近发现的抗炎作用。高灵敏度质谱仪的可用性不断提高，可以定量检测人血浆样品中低丰度的生物标志物，例如15d-PGJ ₂。在此，采用灵敏的LC-MS / MS方法测定15d-PGJ ₂建立了。该方法已根据美国食品和药物管理局的指导进行了验证，并在控制不佳的糖尿病患者的血浆样本中进行了测试，这些患者被认为是促炎性疾病。在甲醇沉淀后，用乙酸乙酯通过易于使用的液-液萃取来完成15d-PGJ _2的萃取。15d-PGJ ₂的定量下限为2.5 pg mL ^-1，线性（R ²  = 0.998）确保在2.5到500 pg mL ^-1之间。通过使用两个单独的质量跃迁（定性剂和定量剂）确保了选择性。在日间和日内分析中验证了准确性和准确性，变异系数分别低于11.8％（日内）和14.7％（日内）。在HbA _1C > 9％的糖尿病患者中，与对照血浆相比，血浆中15d-PGJ _2的浓度增加了。15d-PGJ ₂与炎症标志物C反应蛋白负相关。发达的LC-MS / MS方法代表了一种定量检测人血浆样品中高特异性15d-PGJ ₂的新可能性。这可能有助于更好地了解15d-PGJ ₂的潜在抗炎作用 严重的长期促炎性疾病，例如糖尿病，癌症或心血管疾病。