The Pharmacokinetics Of Corydalis Yanhusuo Extract In Mice After Oral Administration

Rhizoma corydalis (Yanhusuo in Chinese), the dried tuber of Corydalis yanhusuo W. T. Wang, is a famous traditional Chinese medicines (TCM) which has been used for blood activation, moving'Qi'(vital energy), and pain relief over thousands of years in China. It has been well known that the alkaloids are major bioactive components of Corydalis yanhusuo. Alkaloids had analgesic effect and other pharmacologic effects, such as anti-depressive, antitumor, antibacterial, anti-inflammatory and antioxidant, etc. At present, many TCM formulations containing Corydalis yanhusuo has been used clinically in headache, coronary heart disease, gastroenteritis, gastric ulcer and other diseases. The determination of the concentration of the active ingredient in the blood and the tissue in vivo is beneficial to the rational use of the drug. In this work, we have successfully developed a rapid and sensitive method to simultaneously determine the components and contents of the alkaloids after administration by high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-MS/MS). The method was successfully applied to investigate the pharmacokinetic of the fourteen alkaloids, including an aporphine (oxoglaucine), a protopine (protopine), five tertiary alkaloids (corydaline, tetrahydroberberine, tetrahydropalmatine, tetrahydrocolumbamine and tetrahydrocoptisine) and seven quaternary alkaloids (columbamine, palmatine, berberine, epiberberine, coptisine, jatrorrhizine and dehydrocorydaline) after oral administration of corydalis yanhusuo extract in mice plasma, brain, heart, liver and kidney.1. Simultaneous determination of fourteen alkaloids in mice plasma by HPLC-MS/MS after oral administration of corydalis yanhusuo extractIn this study we developed and validated an HPLC-MS/MS method for the simultaneous determination of the fourteen alkaloids to study its pharmacokinetic profiles in mice plasma. The HPLC analysis was performed on a ZORBAX Eclipse XDB-C18 column (2.1 × 100 mm,3.5 ?m) by using a gradient elution program with a mobile phase consisting of acetonitrile and water which both contained 0.1% formic acid at a flow rate of 0.3 mL/min. Using nitidine chloride as an internal standard and multiple reaction monitoring (MRM) mode detection. The method validation was strictly carried out according to the FDA Guidance for Industry Bioanalytical Method Validation (2013 Version) and Chinese Pharmacopoeia volume ? guidelines on bioanalytical method validation, the results were within the prescribed limits. Blood samples were collected into heparinized tubes at different time points within 24 h after or before oral administration of 1.25 g/kg corydalis yanhusuo extract to mice. The comparation pharmacokinetic parameters study of twelve alkaloids (the plasma concentration of berberine and epiberberine is under detection limit) showed that most alkaloids can be quickly absorbed into blood, the eliminate of THP in the blood was the fastest.2. The distribution of the fourteen alkaloids in four kinds of mice tissues by HPLC-MS/MS after oral administration of corydalis yanhusuo extractIn this study we developed and validated an HPLC-MS/MS method for the simultaneous determination of the fourteen alkaloids to study its pharmacokinetic profiles in mice tissuse based on blood HPLC-MS/MS method. All values of method validation were within the acceptable limits. Besides, all analytes were proven to be stable under different storage conditions. The accurate and reliable HPLC-MS/MS method was successfully applied to investigate the pharmacokinetic of the fourteen alkaloids after oral administration of 1.25 g/kg corydalis yanhusuo extract in mice brain, heart, liver and kidney. The results showed that most alkaloids in corydalis yanhusuo extract can be rapidly distributed to four tissues and the distribution of all alkaloids in the liver is greatest. The distributions of COP, DH-COR, and PRO in heart were higher. The distribution of COP, DH-COR and PRO in liver was higher. Tertiary alkaloids distributed quicker than quaternary alkaloids and then the concentration of tertiary alkaloids decreased gradually to LLOQ in liver with no obvious redistribution or transformation occurred. However, the quaternary alkaloids had a possibility of redistribution or drug conversion in the liver. The distribution of COP, DH-COR and PRO were higher in kidney.