Development of analytical methodology for simultaneous determination of meta-chlor...
| Grant number: | 12/50595-8 |
| Support type: | Regular Research Grants |
| Duration: | October 01, 2013 - September 30, 2015 |
| Field of knowledge: | Health Sciences - Pharmacy - Medicines Analysis and Control |
| Cooperation agreement: | CNPq - First Projects Program |
| Principal Investigator: | María Segunda Aurora Prado |
| Grantee: | María Segunda Aurora Prado |
| Home Institution: | Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
Abstract
Hypercholesterolemia is a major cause of atherosclerosis and associated diseases such as coronary heart disease, cerebrovascular disease and ischemic vascular disease. Statins are drugs used as first-line treatment of hypercholesterolemic patients, but some patients need higher doses of statins and it increases the risk of adverse events, such as myopathy, which can compromise patient adherence to drug treatment. Ezetimibe is a selective inhibitor of intestinal cholesterol and phytosterols absorption, it is an alternative therapy for treatment of dyslipidemia, without or in association with a statin. The therapeutic monitoring is essential to ensure a treatment safety and effective. The present project aims to develop, optimize and validate a methodology by capillary electrophoresis (CE) and compare it with high performance liquid chromatographic (HPLC) method to be applied for simultaneous quantification of simvastatin and ezetimibe and / or ezetimibe in pharmaceutical formulations and in biological samples. To date, there is no method by CE for the simultaneous determination of ezetimibe and simvastatin (in association) in biological samples. Thus establishing new alternatives with advantages for the quality control of pharmaceuticals and can be used for evaluation in clinical and pharmacokinetic studies. For this study, 50 tablets and plasma samples from 50 patients with dyslipidemia treated with statins in combination or not with ezetimibe will be used. The drugs will be identified, separated and quantified by HPLC and CE methods. The liquid chromatography-mass spectrometry method will be used to identify plasma's metabolites. The validation of the analytical methods will be performed according International Conference on Harmonization and United States Pharmacopeia guidelines (specificity, accuracy, precision (repeatability and intermediate precision), linearity, range, limit of detection (LOD), limit of quantification (LOQ) and robustness). The obtained data will be compared by statistical tests such as t, F and ANOVA tests. It is hoped to identify the method of quantification of lipid-lowering with better analytical performance and wider use in different samples, with lower operating costs and environmental impact. The results will contribute to improve the analytical quality control in the pharmaceutical industry, and assist the bioavailability studies and therapeutic monitoring useful in assessing the efficacy and safety of pharmaceuticals. (AU)