| Scutellarin is a flavonoid compound with the molecular formula C21H18O12,which is the main active ingredient of the Chinese medicine Erigeron breviscapus and plays an important role in the treatment of cardiovascular and cerebrovascular diseases such as cerebral thrombosis,hemiplegia after stroke,angina pectoris,coronary heart disease,etc.However,the low bioavailability of its preparations has limited its clinical application.A large number of studies have shown that the complex formed by the reaction of flavonoids with metal ions can not only increase the solubility of flavonoids but also enhance the biological activity of flavonoids.A large number of documents indicated that the pathogenesis of cardiovascular and cerebrovascular diseases was related to magnesium deficiency,which also affected the prognosis of the disease,suggested that magnesium played a very important role in the prevention and treatment of cardiovascular and cerebrovascular diseases.It is reported that the salt synthesized by flavonoids and metal ions was reduced to the original substance under the action of gastric acid,which was not suitable for oral administration.However,due to the synthesis of salts had good solubility,the injection can be considered.Based on this,the research group prepared the scutellarin magnesium salt in the early stage to improve the solubility of scutellarin,and conducted intravenous injection of scutellarin magnesium salt to study its effect against the cerebral ischemia-reperfusion injury.As a result,it was found that the magnesium salt of scutellarin was significantly better than scutellarin.After determined the efficacy of the scutellarin magnesium salt,this study mainly investigated the pharmacokinetics and tissue distribution characteristics of intravenous scutellarin magnesium salt in rats,and compared the scutellarinmagnesium salt and scutellarin about the pharmacokinetic parameters and tissue distribution characteristics,provided a certain experimental basis for the use and development of scutellarin magnesium salt.Objectives:To establish an accurate and reliable detection method to investigate the pharmacokinetic characteristics and tissue distribution of intravenously administered scutellarin magnesium salt in rats,and to compare the pharmacokinetic parameters and tissue distribution of scutellarin magnesium salt and scutellarin,provided certain experimental data and scientific basis for the pharmacodynamic mechanism and toxicology research of intravenous injection of scutellarin magnesium salt.Methods:1?The scutellarin magnesium salt?10,20,40 mg/kg?and scutellarin?19.49 mg/kg?were administered via tail vein injection,and blood was taken from the ocular vein at different time points within 24 hours.UPLC-MS/MS method was used to determine the drug concentration in plasma at each time point,and the plasma drug concentration-time?C-T?curve was drawn.The pharmacokinetic parameters were calculated by non-compartmental model analysis of DAS 3.0 software,and statistical analysis was performed using SPSS 19.0 software.2?After injected with scutellarin magnesium salt and scutellarin,the rats were anesthetized at different time points within 8h,and the brain,heart,liver,lung,kidney,stomach,fat,small intestine,large intestine,adrenal gland,testis,ovaries,uterus,spleen,thymus,pancreas,muscle tissue were separated.To investigate the distribution of scutellarin magnesium salt and scutellarin in rats after tail vein injection,UPLC-MS/MS method was used to determine the drug concentration in different tissues at each time point and DAS 3.0software was used to analyze and calculate tissue dynamics parameters.SPSS19.0 software was used for statistical analysis.3?Chromatographic conditions: ACQUITY UPLC BEH C18 column?2.1×50 mm,1.7?m,Waters Corp.,USA?at a column temperatuer of 40 ?;Amixture of solvent A?containing 0.1% formic acid in water?,B?acetonitrile?,C?methanol?was used as the mobile phase at a flow rate 0.3m L/min under gradient elution program as follows: 0 ? 0.5min,78% A;0.5 ? 0.6 min,78% ?70% A;0.6 ? 1.5 min,70% A;1.5 ? 1.6 min,70%?10% A;1.6 ? 3.0 min,10% A;3.0 ? 3.1 min,10% ? 78% A;3.1 ? 5.0min,78% A,B?acetonitrile?0? 5min,10%.MS conditions: it was set in negative multiple reaction monitoring?MRM?mode.And the MS transitions were m / z 461.0?284.9for scutellarin magnesium salt and m / z 301.2?151.0 for quercetin?IS?.Results:1?The dose is positively correlated with AUC?0-t?and C0 in the range of10 ? 40 mg/kg,scutellarin magnesium salt had linear kinetics characteristics in rats.The parameters of AUC?0-??,AUMC?0-??,VRT?0-??,C?last,t1/2z in the scutellarin magnesium salt group were higher than those ofscutellarin group,but the differences in parameters between the two groups were not statistically significant.2?The scutellarin magnesium salt and scutellarin were widely distributed in various tissues.The drug was mostly distributed in the kidney,but less in the brain and spleen.Tissue pharmacokinetic parameters showed that the AUC?0-t?of scutellaria baicalin magnesium salt was significantly higher than that of the scutellarin in spleen and ovary?P < 0.05?.But the AUC?0-t?of scutellaria baicalin magnesium salt was lower than that of the scutellarin in the thymus?P < 0.05?.In addition,the AUC?0-t?of the scutellaria magnesium salt was slightly higher than that of the scutellaria group in the brain,heart,spleen,stomach,small intestine,large intestine,pancreas,fat,muscle,and uterus.The AUC?0-t?of the scutellaria magnesium salt was 1.17 times that of the baicalin in the brain tissue.8h after injection,the content of scutellaria and scutellaria magnesium salt were 1.30 ± 0.68?ng/mg?and 0.32± 0.16?ng/mg?in brain tissue.Compared with scutellaria and scutellaria magnesium salt can maintained low concentration in brain tissue for a longer time.Conclusions:The established analytical method was simple,accurate,and reliable.with high sensitivity and strong specificity,and can be used to determine the concentration of scutellaria magnesium salt in rat plasma and tissue samples by UPLC-MS/MS,which can meet the pharmacokinetics of scutellaria magnesium salt in rats and organization distribution research.After injection,the scutellaria magnesium salt and scutellaria were quickly absorbed in the body.The distribution of each tissue was relatively wide,and the metabolism was also eliminated quickly.The pharmacokinetic characteristics of the two groups in rats were similar,but there were certain differences in tissue distribution.The AUC?0-t?of scutellaria magnesium salt and scutellaria were obviously different in spleen,ovary and thymus,the difference was statistically significant.The specific reasons and mechanisms were not yet clear and need to be confirmed by further research.Compared with scutellaria,scutellaria magnesium salt can maintain a low concentration in brain tissue for a longer period of time,which may be the reason why baicalin magnesium salt is better than baicalin in treating the cerebral ischemia-reperfusion injury. |
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