| Abstract | Razgradni produkti fosamprenavira analizirani su brzom metodom tekućinske kromatografije ultravisoke djelotvornosti spregnute s masenom spektrometrijom. Uzorci fosamprenavira podvrgnuti su razgradnji pri različitim uvjetima: u 5 M HCl, u 5 M NaOH, u 30 %-tnom H2O2, izlaganjem svjetlosti tijekom 24 sata, zagrijavanjem 1 sat na 80 °C te 48 sati na 105 °C. Analizom tekućinskom kromatografijom su se provjerili uvjeti i je li došlo do odgovarajućeg stupnja razgradnje te zaključivši da uvjete treba podesiti uzorci su na gore navedenim jačim uvjetima analizirani masenom spektroskopijom. Razgradni produkti su ionizirani pozitivnim načinom ionizacije, a nastali ioni su razdvajani po omjeru mase i naboja. Dobiveni su kromatogrami i maseni spektri razgradnih produkata te su povezani sa strukturama svih razgradnih produkata. Neke od struktura su poznate u literaturi, neke su predviĎene Zeneth računalnim programom, a neke do sad nepoznate su predloţene i zahtijevaju dodatnu potvrdu daljnim analizama. Sve strukture su nacrtane u programu Chemdraw i prikazane zajedno s molekulskom masom koju računa sam program. Fosamprenavir se najviše razgradio u oksidativnim uvjetima gdje je nastalo nekoliko novih i nepoznatih produkata masa: 516,15, 602,19, 316,11, 616,17, 560,18, 504,22, 536,21. Razgradnji s HCl je svojstven nastanak produkta mase 620,16, a bazičnom hidrolizom je nastao produkt mase 418,18. Pri svim uvjetima razgradnje nastali su produkti masa 472,17 i 506,23 poznati u literaturi te prisutni i u netretiranom uzorku fosamprenavira. |
| Abstract (english) | The degradation products of fosamprenavir were analyzed using a fast method of ultra-high performance liquid chromatography associated with mass spectrometry. Fosamprenavir samples were degraded under different conditions: in 5 M HCl, in 5 M NaOH, in 30 % H2O2, exposure to light for 24 hours, heating for 1 hour at 80 °C and 48 hours at 105 °C. Liquid chromatographic analysis was used to verify the conditions and an adequate degree of degradation, thus concluding that the conditions should be adjusted, so the samples were analyzed by mass spectroscopy under the above-mentioned stronger conditions. The degradation products were ionized by the positive ionization method and the ions were separated by mass-to-charge ratio. Chromatograms and mass spectra of degradation products have been obtained and connected with the structures of all degradation products. Some of the structures are known in the literature, some have been predicted by the Zeneth software, and some so far unknown are proposed and require additional confirmation by further analysis. All structures are drawn in the Chemdraw program and shown together with the molecular mass calculated by the program itself. Fosamprenavir degraded the most in oxidative degradation conditions where several new and unknown mass products were formed: 516.15, 602.19, 316.11, 616.17, 560.18, 504.22, 536.21. Degradation of fosamprenavir with HCl has resulted in the formation of a product with a mass of 620.16, while basic hydrolysis has resulted in a product mass of 418.18. Products of masses 472.17 and 506.23 were produced under all conditions, known in the literature and present in an untreated sample of fosamprenavir. |
