The Study on Potential Biomarker in Rat After Withdrawal of Cimaterol Using Untargeted Metabonomics

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.