20.500.12556/DKUM-69363 Optimizacija HPLC metode za določanje sorodnih substanc prednisolona v učinkovini Optimization of HPLC method for determination of related substances of prednisolone in active ingredient Analiza vsebnosti sorodnih substanc je nujna v fazi razvoja in proizvodnje zdravila. Pri evropski farmakopejski HPLC - metodi (Ph.Eur.) za določanje sorodnih substanc prednisolona se v praksi pogosto pojavlja težava z doseganjem kriterija za ustreznost sistema. Težava se pojavlja pri slabi ločbi prednisolona in njegove sorodne substance hidrokortizona (nečistota A), ki sta si strukturno zelo podobna. Ph.Eur. HPLC metoda za določanje sorodnih substanc prednisolona je bila razvita na kromatografski koloni Venusil AQ C18, 150 mm x 4,6 mm, 3 m delci, ki smo jo testirali kot izhodišče naše nadaljne optimizacije. V nadaljevanju magistrskega dela smo poskušali optimizirati Ph.Eur. metodo na kolonah s stacionarno fazo C18 drugega proizvajalca v okviru dovoljenih odstopanj od Ph.Eur., in nato poskušali razviti in predlagati novo metodo. V magistrskem delu so doseženi vsi predhodno zastavljeni cilji. Prikazana je optimizirana metoda v okviru dovoljenih odstopanj od Ph.Eur. s katero smo na koloni Gemini C18, 150 mm x 4,6 mm, 3μm delci dosegli kriterij za ustreznost sistema - razmerje vrh/dolina Hp/Hv = 10,5. Z optimizirano metodo dosežemo precej izboljšan rezultat v primerjavi z referenčnim kromatogramom Ph.Eur. metode na koloni Venusil AQ C18, 150 mm x 4,6 mm, 3 m delci, kjer je doseženo razmerje Hp/Hv = 7,0. V magistrskem delu je predstavljena tudi nova razvita metoda s katero smo dosegli zelo dobro ločbo sorodnih substanc in ločitev prednisolona in nečistote A skoraj na bazni liniji (Hp/Hv = 21,0). An analysis of related substances is necessary in the development and production phase of the drug. In practice, in the implementation of Ph.Eur. HPLC method for the determination of related substances of prednisolone, we often encounter a problem with achieving a system suitability criteria. The problem is with the separation of the peaks prednisolone and its related substance hydrocortosone (impurity A), which are structurally very similar. Ph.Eur. HPLC method for the determination of related substances of prednisolone was developed on the chromatography column Venusil AQ C18, 150 mm x 4.6 mm, 3 μm particles, which we tested as the starting point for our further optimization. In the continuation of the master's thesis we tried to optimize Ph.Eur. method on columns with the C18 stationary phase of the other manufacturers within the allowable adjustments to European pharmacopeia methods., and then tried to develop a new method. All previously determined goals in the master's thesis have been achieved. In the master's paper is presented an optimized method (within the allowable adjustments to European pharmacopeia methods) on the column Gemini C18, 150 mm x 4.6 mm, 3 μm particles, with which we reached the criteria for the system suitability, the ratio peak/valley – Hp/Hv = 10,5. With the optimized method, we achieve a significantly improved result compared to the reference chromatogram obtained with the Ph.Eur. method on the column Venusil AQ C18, 150 mm x 4.6 mm, 3 μm particles, where the Hp/Hv ratio is 7,0. In the master's paper, a new developed method is introduced to achieve a very good separation of related substances and the separation of prednisolone and impurity A, which is almost on the base line (Hp/Hv = 21,0). prednisolon sorodne substance HPLC Ph.Eur. optimizacija HPLC metode razvoj HPLC metode prednisolone related substances HPLC Ph.Eur. HPLC method optimization HPLC method development true true false [N. Ledinek] Slovenski jezik Angleški jezik Magistrsko delo/naloga 2018-01-12 01:43:18 2018-01-26 13:39:48 2022-08-01 17:22:05 2019-07-11 17:29:26 2018 0 Maribor 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 543.544.17:543.544.5(043.2) 21155862 URN:SI:UM:DK:X6GC0ANK MAG_Ledinek_Nina_2018.pdf MAG_Ledinek_Nina_2018.pdf 1 92510F61978AAB20412224C34B2859EA afedc1271b5909bcec42b8cd5d3f1399deb0ab62c9f51c69cf94ad566d77e3d0 9da61707-7c0f-11eb-bb7a-00155d0001ca 20.500.12556/dkum/deae24d5-d03f-4dd5-843f-f21f2f5f3902 https://dk.um.si/Dokument.php?lang=slv&id=121477 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0