The present study was performed to screen the potential biomarkers of cimaterol in rat, using an untargeted metabonomics approach. The liver and serum samples were analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC–QTOF-MS) after treatment of rats with cimaterol. The principal component analysis (PCA) and orthogonal projection to latent structures squares-discriminant analysis (OPLS-DA) were applied to distinguish control group (CG) and experimental group (EG). Eleven potential biomarkers existing in both liver and serum samples were obtained, including 2-Indolecarboxylic acid, 1,2-Dioleoyl PC, xanthine, PC(14:0/20:1(11z)), hexadecanedioic acid,PE(22:4(7Z,10Z,13Z,16Z)/14:0),lysoPE(0:0/18:2(9Z,12Z)), fluorometholone acetate, PE(MonoMe(9,5)/MonoMe(13,5)), chenodeoxyglycocholic acid and ethyl abietate. These potential biomarkers were involved in pantothenate and CoA biosynthesis, synthesis and degradation of ketone bodies, sphingolipid metabolism, vitamin B6 metabolism, linoleic acid metabolism and arachidonic acid metabolism. After withdrawal of cimaterol, the duration time of fluorometholone acetate in serum and liver of rats was both more than 15 days, which were much longer than that of parent drugs cimaterol. Therefore, the fluorometholone acetate was more suitable for supervising to the illegal use of cimaterol from the views of accessibility and accuracy. This study can provide the theoretical basis for the accurate monitoring method of cimaterol based on potential biomarker fluorometholone acetate.

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非靶向代谢组学对大鼠停用西马特罗后潜在生物标志物的研究

本研究使用非靶向代谢组学方法筛选大鼠中西马特罗的潜在生物标志物。用西马特罗处理大鼠后，通过超高效液相色谱联用四极杆飞行时间质谱（UHPLC-QTOF-MS）分析肝脏和血清样品。应用主成分分析（PCA）和潜在结构平方判别分析（OPLS-DA）的正交投影来区分对照组（CG）和实验组（EG）。获得了肝脏和血清样品中存在的 11 种潜在生物标志物，包括 2-吲哚羧酸、1,2-二油酰 PC、黄嘌呤、PC(14:0/20:1(11z))、十六烷二酸、PE(22:4 (7Z,10Z,13Z,16Z)/14:0),lysoPE(0:0/18:2(9Z,12Z)), 氟米龙醋酸酯, PE(MonoMe(9,5)/MonoMe(13,5)) , 鹅脱氧甘胆酸和松香酸乙酯。这些潜在的生物标志物涉及泛酸和 CoA 的生物合成、酮体的合成和降解、鞘脂代谢、维生素 B6 代谢、亚油酸代谢和花生四烯酸代谢。西马特罗停药后，醋酸氟米龙在大鼠血清和肝脏中的持续时间均超过15天，远长于母体药物西马特罗。因此，从可及性和准确性的角度来看，醋酸氟米龙更适合对西马特罗的非法使用进行监管。该研究可为基于潜在生物标志物醋酸氟米龙的西马特罗的准确监测方法提供理论依据。酮体的合成和降解、鞘脂代谢、维生素B6代谢、亚油酸代谢和花生四烯酸代谢。西马特罗停药后，醋酸氟米龙在大鼠血清和肝脏中的持续时间均超过15天，远长于母体药物西马特罗。因此，从可及性和准确性的角度来看，醋酸氟米龙更适合对西马特罗的非法使用进行监管。该研究可为基于潜在生物标志物醋酸氟米龙的西马特罗的准确监测方法提供理论依据。酮体的合成和降解、鞘脂代谢、维生素B6代谢、亚油酸代谢和花生四烯酸代谢。西马特罗停药后，醋酸氟米龙在大鼠血清和肝脏中的持续时间均超过15天，远长于母体药物西马特罗。因此，从可及性和准确性的角度来看，醋酸氟米龙更适合对西马特罗的非法使用进行监管。该研究可为基于潜在生物标志物醋酸氟米龙的西马特罗的准确监测方法提供理论依据。醋酸氟米龙在大鼠血清和肝脏中的持续时间均超过15天，远长于母体药物西马特罗。因此，从可及性和准确性的角度来看，醋酸氟米龙更适合对西马特罗的非法使用进行监管。该研究可为基于潜在生物标志物醋酸氟米龙的西马特罗的准确监测方法提供理论依据。醋酸氟米龙在大鼠血清和肝脏中的持续时间均超过15天，远长于母体药物西马特罗。因此，从可及性和准确性的角度来看，醋酸氟米龙更适合对西马特罗的非法使用进行监管。该研究可为基于潜在生物标志物醋酸氟米龙的西马特罗的准确监测方法提供理论依据。

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