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ObjectiveTo establish a high performance liquid chromatography （HPLC） for simultaneous determination of baicalin magnesium and baicalein in rat plasma and tissues， and to investigate the effect of acute liver injury on pharmacokinetics and tissue distribution of baicalin magnesium in rats. MethodAcute liver injury rat model was induced by carbon tetrachloride （CCl4）. Normal rats and acute liver injury model rats were given an equal dose （287.31 mg·kg-1） of baicalin magnesium aqueous solution by intragastric administration， the orbital blood was collected at different time points， and HPLC was used to simultaneously determine the concentrations of baicalin magnesium and baicalein in rat plasma at each time point， the concentration-time curves were drawn， the pharmacokinetic parameters were calculated with DAS 3.0， and SPSS 23.0 was used for statistical analysis. After oral administration of baicalin magnesium aqueous solution， HPLC was used to simultaneously determine the contents of baicalin magnesium and baicalein in rat liver， lung， kidney， stomach， brain and small intestine at different time points， the mobile phase was 0.1% phosphoric acid aqueous solution-methanol， and the detection wavelength was 278 nm. ResultIn the acute liver injury model group， the peak concentration （Cmax） of baicalin magnesium was 0.58 times that of the normal group， the area under concentration-time curve （AUC0-t） was 0.5 times that of the normal group （P<0.05）， the apparent volume of distribution （Vd） was 2.3 times that of the normal group （P<0.05）， and baicalein is almost undetectable in plasma. The content of baicalin magnesium in liver， stomach and brain of the acute liver injury model group was higher than that of the normal group at each time point， while the content of baicalin magnesium in the samples of lung at 8 h， kidney at 8 h and 12 h， and small intestine at 0.333 h was lower than that of the normal group. The content of baicalein in lung， stomach and small intestine of the model group was higher than that of the normal group at each time point， while the content of baicalein in the tissue samples of liver at 6， 8 h and kidney at 0.333， 4， 6 h was lower than that in the normal group， and baicalein could hardly be detected in the brain. ConclusionAfter intragastric administration of the same dose of baicalin magnesium aqueous solution， acute liver injury induced by CCl4 can affect the pharmacokinetics and tissue distribution characteristics of baicalin magnesium in rats， and there is biotransformation of baicalin magnesium and baicalein in liver， lung， kidney， stomach and small intestine.
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Objective:To study on the pharmacokinetics and tissue distribution of baicalin magnesium salt in rats after tail vein injection,and compare pharmacokinetic differences between baicalin magnesium salt and baicalin. Method:After tail vein injection of baicalin magnesium salt and baicalin,orbital blood was collected at different time points.The drug concentration was measured by HPLC,the drug concentration-time curve was plotted,the pharmacokinetic parameters were calculated with DAS 3.0 software,SPSS 19.0 software was used for statistical analysis.At the same time,the drug distribution in heart,liver,spleen,lung and kidney was measured at different time points after tail vein injection of baicalin magnesium salt. Result:When the dose of baicalin magnesium salt was 25-100 mg·kg-1,area under the curve(AUC0-t and AUC0-∞) showed a good linear relationship with the dose(r>0.95),but most of the other pharmacokinetic parameters had no significant difference between different dose groups.The mean residence time(MRT0-t) of medium dose group of baicalin magnesium salt was significantly higher than that of equal molar dose group of baicalin.After intravenous injection of baicalin magnesium salt,the drug concentration was the highest in each tissue at 0.25 h,and the concentration of target component decreased rapidly at 0.75 h.The distribution of target component in kidney was the most,followed by lung. Conclusion:After injection,the baicalin magnesium salt can be rapidly distributed and quickly eliminated in vivo,which is mainly excreted from the kidney.
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AIM To investigate the effects of aqueous extraction at normal temperature,40 ℃,and water boiling on total coumarins extract of Angelicae dahuricae Radix.METHODS For the extracts Ⅰ-Ⅳ obtained by ethanol reflux extraction and three aqueous extraction preprocessing methods,respectively,UV and HPLC were adopted in the content determination of total coumarins and imperatorin,then the powder properties and dissolution rates were compared.RESULTS The contents of total coumarins in four extracts were 3.98％,6.03％,6.81％ and 4.46％,while those of imperatorin were 0.633％,0.540％,0.465％ and 0.155％,respectively.The angles of repose were 48.455°,42.587°,42.689° and 42.024° with the bulk densities of 0.214,0.324,0.316 and 0.354 g/cm3,respectively.Within 100 min,extract Ⅰ demonstrated higher moisture adsorption rate and equilibrium moisture absorption content than the other three extracts.The accumulative dissolution rates of various extracts were much higher than that of medicinal material fine powder within 120 min.CONCLUSION All the three aqueous extraction preprocessing methods can obviously improve the powder properties of total coumarins extract of A.dahuricae Radix and increase the dissolution rate of medicinal material fine powder.
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Aconiti Lateralis Radix (Fuzi) is a toxic traditional Chinese medicine with definite efficacy. In order to improve the quality control of its different prepared products and ensure the security in clinic, it is significant to establish a method of quality evaluation related to clinic adverse effects. Aiming at the important biological marker of early cardiac toxicity reaction, there was no method to detect it. In this manuscript, a novel approach for measuring the minimal toxic dose (MTD) of premature ventricular contractions (PVC) poisoning of rats was established. Then, the determination methodology and conditions were optimized to meet the needs of the quality and biological assessment, including animal sex, weight, stability of standards and test solutions. Using this method, the MTD value of different Fuzi products were determined, such as Heishunpian, Baifupian, Zhengfupian, Baofupian, and Paotianxiong. The results showed that the MTD of Fuzi was significantly decreased after detoxification processed (P<0.05) and the MTD of Heishunpian, Zhengfupian, Baofupian and Baifupian was as much as 15.76, 22.36, 19.65 and 20.97 times to that of unprocessed Shengfuzi. In addition, Paotianxiong could not induce PVC in rats, which indicated that Paotianxiong was nontoxic and safe.This method could appropriately reflects the cardiotoxity of Fuzi and its prepared samples. Together with the chemical composition analysis, the contents of diester alkaloids were explored including aconitine, mesaconitine and hypaconitine as well as monoester alkaloids in Fuzi and its prepared products were significantly associated with PVC. Furthermore, there may be some components undetermined facilitating arrhythmia to be worth exploring. This research provides an overall and comprehensive approach to diagnose early clinical cardiotoxity and control the quality of Fuzi, which could not only be a complementary solution for the chemical evaluation, but a new method to ensure its efficacy and security of clinical application.
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Sanhuang tablets is one of common traditional Chinese patent preparation, it has effects of clear fever, detoxifcation, dispel inflammation, purgation. It was contained in the ministerial standards of Ministry of Health in 1997, and was contained in Chinese pharmacopoeia version 1 of 2000 and 2005. Its improvement of dosage form, preparation technique, quality analysis, pharmacology and clinical usage were reviewed in this paper.