| Diabetes mellitus?DM?is a common endocrine and metabolic disease characterized by prolonged high blood glucose levels caused bydysfunction or defects within the insulin secretion system.In addition to the typical"three more and one less"symptoms,long-term hyperglycemia may cause a series of complications including macrovascular disease and microvascular disease,and seriously endanger human health.Therefore,effective treatment of diabetes is imperative.Compared with western medicine,traditional Chinese medicine has the characteristics of stable curative effect,mildness and low toxicity.In recent years,more and more traditional Chinese medicine ingredients with hypoglycemic activity have been reported,and aucubin?AU?is one of them.There have been studies reporting that AU can lower blood sugar.At present,the research on the pharmacokinetics,biological activity and tissue distribution of AU is becoming more and more perfect,but there are few reports on the pharmacokinetics of AU in the state of diabetes.Therefore,this study intends to use the type 1diabetic rat model to explore the pharmacokinetic behavior of AU in the diabetic state and the difference in pharmacokinetics of AU between normal rats and type 1 diabetic rats.In the study of pharmacokinetics of AU,the effective extraction and analysis of AU in samples is also particularly important.In this study,the supramolecular solvent?SUPRAS?dispersive liquid-liquid microextraction?DLLME?combined with ultra high performance liquid chromatography-tandem mass spectrometry?UPLC-MS/MS?was used to detect the AU concentration in serum.After the protein was purified by protein precipitation,SUPRAS formed by 1.0 mL of pentanol,4.0 mL of tetrahydrofuran and 35.0 mL of ultrapure water was used for liquid-liquid microextraction.The extraction time was 2.5 min.Acetonitrile-10 mmol/L ammonium formate aqueous solution?pH=3.5?was used as the mobile phase for gradient elution.Multi-reaction monitoring mode?MRM?was used for detection in electrospray?ESI?positive ion mode.The results showed that under the optimal experimental conditions,AU showed a good linear relationship?r>0.999?in the range of 3 ng/mL-10?g/mL,LOD was 1 ng/mL,and LOQ was 3ng/mL.The recovery rates at three addition levels of low?10 ng/mL?,medium?1000 ng/mL?and high?10000 ng/mL?were 103.60%-119.33%,and the relative standard deviations were0.33%-14.27%.It shows that the pretreatment method and instrument analysis method have low quantitation limit,high recovery rate and good repeatability,and can be used for the detection of AU in serum.The optimized pretreatment method and established analysis method were used to detect and analyze the concentration of AU in serum samples at different time points after intraperitoneal injection of AU 5 mg/kg in normal rats and type 1 diabetic rats.DAS 3.0performs data analysis on non-compartmental models.the pharmacokinetic parameters of AU in type 1 diabetic rats were different from those in normal rats except tmax.The Cmax?AUC?0–t?and AUC?0-??of AU in type 1 diabetic rats were increased,and the t1/2?MRT?0-???Vz/F and CLz/F was decreased.It was suggested that the status of type 1 diabetes would affect the pharmacokinetic behavior of AU,which provided a reliable scientific basis for the supplement of the pharmacokinetic characteristics of AU and the rational use of drugs in the treatment of type 1 diabetes. |
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