"1A8689" Dotaz Zobrazit nápovědu
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
Přeruš. str. : il., tab. ; 30 cm
Statins are administered to a wide range of individuals on an empirical basis. Investigation of the phenotype and genotype influences on treatment response will allow a more tailored use of these drugs. The development and application of new biotechnological methods to study relationship of phenotypes, genotypes and response to statin therapy upon lipoprotein metabolism will be used: i) distribution of statins and its metabolites in serum lipoprotein and cell membranes, ii) vitamin E content in serum and cell membranes, iii) lipoperoxidation formation and antioxidant consumption
Statiny jsou široce používaná léčiva podávaná pacientům často na empirické bázi. Zkoumání vlivu fenotypu a genotypu na jejich léčebné účinky umožní efektivnější používání těchto léčiv. Vývoj a aplikace nových biotechnologických a diagnostických metod kesledování vztahů mezi fenotypem, genotypem a odezvou na léčbu statiny ve vztahu k metabolismu lipoproteinů bude využito pro: i) objasnění distribuce statinů a jejich metabolitů v jednotlivých lipoproteinových frakcích a buněčných membránách ii) sledováníobsahu vitaminu E v séru a buněčných membránách iii) sledování lipoperoxidace a spotřeby antioxidantů
- MeSH
- ateroskleróza MeSH
- fenotyp MeSH
- genetické jevy MeSH
- genotyp MeSH
- hypercholesterolemie MeSH
- hyperlipidemie MeSH
- peroxidace lipidů MeSH
- statiny farmakologie MeSH
- tokoferoly MeSH
- vysokoúčinná kapalinová chromatografie využití MeSH
- Konspekt
- Biochemie. Molekulární biologie. Biofyzika
- NLK Obory
- biochemie
- farmacie a farmakologie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
Simvastatin and atorvastatin belong to the group of hypolipidemic drugs, more exactly to the second generation of inhibitors of microsomal 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. They induce a significant reduction in total cholesterol, low-density lipoprotein cholesterol and plasma triglycerides, therefore they are widely used in the treatment of hypercholesterolemia even of its severe form-familiar hypercholesterolemia. Simvastatin and atorvastatin as the most widely used statins in clinical treatment and their hydroxy-acid/lactone forms were determined by means of UPLC in connection with triple quadrupole mass spectrometer. Deuterium labeled reference standard compounds were used as internal standards for the quantitation. Separation was performed on Acquity BEH C18 (100 mm x 2.1 mm, 1.7 microm) using gradient elution by mobile phase containing acetonitrile and ammonium acetate pH 4.0, which is convenient in order to prevent interconversion of analytes. ESI in positive mode was used for the ionization of all compounds. Two SRM (selected reaction monitoring) transitions were carefully optimized for each analyte in order to get high sensitivity and selectivity. SPE on Discovery DSC-18 was used as a sample preparation step. Intra-day precision was generally within 10% RSD, while inter-day precision within 15% RSD. Method accuracy expressed as recovery ranged from 75 to 100%. The method was validated with the sensitivity reaching LOQ 0.08-5.46 nmol/l and LOD 0.01-1.80 nmol/l in biological samples. Atorvastatin, simvastatin, its metabolites and hydroxy-acid/lactone forms were monitored in human serum and in lipoprotein fractions (LDL, HDL and VLDL) at patients with end stage renal diseases.
- MeSH
- anticholesteremika krev terapeutické užití MeSH
- hypercholesterolemie farmakoterapie MeSH
- kyseliny heptylové krev terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- pyrroly krev terapeutické užití MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- simvastatin krev terapeutické užití MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- hodnotící studie MeSH
- práce podpořená grantem MeSH
CAD (charged aerosol detector) has recently become a new alternative detection system in HPLC. This detection approach was applied in a new HPLC method for the determination of three of the major statins used in clinical treatment-simvastatin, lovastatin and atorvastatin. The method was optimized and the influence of individual parameters on CAD response and sensitivity was carefully studied. Chromatography was performed on a Zorbax Eclipse XDB C18 (4.6 mm x 75 mm, 3.5 microm), using acetonitrile and formic acid 0.1% as mobile phase. The detection was performed using both CAD (20 pA range) and DAD (diode array detector-238 nm) simultaneously connected in series. In terms of linearity, precision and accuracy, the method was validated using tablets containing atorvastatin and simvastatin. The CAD is designated to be a non-linear detector in a wide dynamic range, however, in this application and in the tested concentration range its response was found to be perfectly linear. The limits of quantitation (0.1 microg/ml) were found to be two times lower than those of UV detection.
- MeSH
- financování organizované MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- MeSH
- finanční podpora výzkumu jako téma MeSH
- Publikační typ
- abstrakty MeSH
