Pharmacokinetics and Tissue distribution study of the initial Calcium Sensitizer-M6 by HPLC-UV metho

来源 :2017年广东省药师周大会 | 被引量 : 0次 | 上传用户:gaoqiongfang
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  Piperphentonamine hydrochloride(PPTA)is a new calcium sensitizer,which could increase cardiotonic functions through enhancing the sensitivity of myocardial contraction protein to Ca2+instead of increasing concentration of Ca2+in myocardial cells.Besides,it could inhibit the intracellular Ca2+overload induced by anoxia-oxygen recovery and reduce myocardial consumption of oxygen.These effects provide protection to cardiac muscle against ischemia-reperfusion induced injury.PPTA processed a very fast metabolic rate.While the M6,the metabolite of PPTA,has different characteristic and shows more chance of other clinical application.We aim to establish a fast、convenient and effective HPLC method for the concentration of M6 and study the pharmacokinetic and Tissue distribution of M6 in rat.The chromatographic separation was achieved on a C18 column using isocratic elution in this study.The whole analysis lasted for 15 min at the wavelength of 265 nm,and the isocratic flow rate was 1.0 mL/min constantly.Both accuracy and precision were satisfactory and the correlation coefficient of the standard curve was r > 0.999,satisfying our concentration test.Concentration-time curve was drawn,and pharmacokinetic parameters were calculated by PKsolover software.The pharmacokinetics study of M6 indicated its prolonging pharmacokinetics parameters such as T1/2 and MRT,approximately 50 times more than those of pro-drug PPTA,but had closed CL rate.Tissue distribution study implied M6 can get through the blood-brain barrier.All characteristics showed its potential clinical application.
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