Application Of HPLC-MS/MS In Clinical Pharmacokinetics Study Of Nifedipine And Amlodipine

Hypertension is a very common diseases around the world, the prevalence rate is up to 10 and 20 percent,and it can cause the lesion to cerebrovascular,the heart and the kidney,which is the main danger diseases to the Health of Human Beings.With the development of our economic and the increase of people's living standards,Hypertension is increasingly becoming an important public health problem and the research of antihypertensive drugs also seems especially important.Nifedipine and Amlodipine are both dihydropyridine calcium antagonist,which is a very important antihypertensive drugs.This article established a HPLC-MS/MS method for determining of Nifedipine and Amlodipine in human plasma and investigating its pharmacokinetics and bioequivalence,in order to provide evidence to guide clinical rational administration for the sustained-release nifedipine(â…¡) of ZHEJIANG WEIKANG PHARMA CEUTICAL Co.,LTD. and the amlodipine besylate tablets of HUBEI HIDRAGON PHARMA CEUTICAL Co.,LTD..The first part described quantitative determination of nifedipine in human plasma by HPLC-MS/MS and its application in bioequivalence evaluation of two nifedipine preparations.The plasma samples were precipitated with acetonitrile,the chromatographic separation was achieved with the mobile phase of a mixture of methanol and 10mM ammonium acetate in 0.2% formic acid(66:34,v/v),using carbamazepine as internal standard(IS).The linear range was 1.003⁷9.56μg·L^-1,and the limit of determination was 1.003μg·L^-1.The RSD of inter-day and intra-day was less than 15%.The method is simple,sensitiv,accurate and reproducible.It is applicable for pharmacokinetic study of nifedipine.Nifedipine concentration was determined after a random crossing oral administration in 23 healthy male volunteers.The pharmacokinetic parameter was calculated by the software of DAS 2.1.1,It suggested that the two preparations of nifedipine were bioequivalent.The second part described quantitative determination of amlodipine in human plasma by HPLC-MS/MS and its application in bioequivalence evaluation of two amlodipine preparations . The plasma samples were extracted by aether after alkalify , the chromatographic separation was achieved with the mobile phase of a mixture of methanol and water in 0.1% formic acid(17:13,v/v),using carbamazepine as internal standard(IS).The linear range was 0.1056¹4.08μg·L^-1,and the limit of determination was improved to 0.1056μg·L^-1.The run time for each sample was only three minutes,the analysis speed was improved greatly.This method was easy to process and more specific.The validation data suggested that the accuracy and precision of this method were acceptable;rate of extraction was stable and high.No matrix effect was found and it is already applied for pharmacokinetic study of amlodipine successfully.Amlodipine concentration was determined after a random crossing oral administration in 20 healthy male volunteers.The pharmacokinetic parameter was calculated by the software of DAS 2.1.1,It suggested that the two preparations of nifedipine were bioequivalent.