@conference{
author = "Miličević, Maja and Crevar, Milkica and Ivković, Branka and Džudović, Jelena",
year = "2022",
abstract = "Rivaroxaban belongs to the group of direct oral anticoagulants (DOAC), drugs used to
prevent and treat venous thrombosis and venous thromboembolism. Drugs from this group
are considered safer than vitamin K antagonists. In case of overdose, their most significant
side effect is bleeding. Given the great toxicological significance, it is very important to
develop an analytical method for quantification of this drug in biological samples. The liquid
chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of
rivaroxaban content in plasma samples was optimized and validated. Plasma samples were
prepared by protein precipitation with cold acetonitrile. Carbamazepine was used as an
internal standard. The analysis was performed on an Infinity Lab Poroshell 120 EC-C18, 4.6
×100 mm, 2.7 μm chromatographic column. The mobile phase consisted of acetonitrile and
0.1% formic acid (50:50, v/v), at a flow rate of 400 μL/min and a column temperature set at
30°C. The autosampler temperature was 4C. The injection volume was 10 μL. Detection of
analytes and internal standard was performed in multireaction monitoring mode (MRM), at
the following ion transitions: 437>145 (m/z) for rivaroxaban, and 237>194 (m/z) for the
internal standard. The optimized method was validated and the obtained parameters
indicate that the method is sensitive, specific, selective, precise and accurate. The samples
were stable under the tested conditions. A validated method has been used to determine the
concentration of rivaroxaban in plasma samples of patients with atrial fibrillation who were
hospitalized under strict medical supervision. Obtained concentrations were in the expected
range., Rivaroksaban pripada grupi direktnih oralnih antikoagulanasa (DOAK), lekova koji se
koriste za prevenciju i lečenje venske tromboze i venske tromboembolije. Lekovi iz ove
grupe se smatraju bezbednijim od antagonista vitamina K. U slučaju predoziranja, njihov
najznačajniji neželjeni efekat je krvarenje. S obzirom na veliki toksikološki značaj, veoma je
važno postojanje analitičke metode za određivanje sadržaja ovog leka u uzorcima biološkog
materijala. Optimizovana je i validirana metoda tečne hromatografije spregnute sa masenom
spektrometrijom (LC-MS/MS) za određivanje sadržaja rivaroksabana u uzorcima plazme.
Uzorci plazme su pripremani metodom precipitacije proteina koja je vršena hladnim
acetonitrilom. Kao interni standard korišćen je karbamazepin. Analiza je izvršena na Infinity
Lab Poroshell 120 EC-C18, 4,6×100 mm, 2,7 μm hromatografskoj koloni. Mobilna faza se
sastojala od acetonitrila i 0,1% mravlje kiseline (50:50, v/v), pri protoku od 400 μL/min i
temperaturi kolone podešenoj na 30°C. Temperatura autosemplera je bila 4C. Injekciona
zapremina je bila 10 μL. Detekcija analita i internog standarda je izvršena u multireakcionom
monitoring modu (MRM), pri sledećim jonskim prelazima: 437>145 (m/z) za rivaroksaban,
odnosno 237>194 (m/z) za interni standard. Optimizovana metoda je validirana i dobijeni
parametri ukazuju da je metoda osetljiva, specifična, selektivna, precizna i tačna. Uzorci su
stabilni pri ispitivanim uslovima. Validirana metoda je primenjena za određivanje
koncentracije rivaroksabana u uzorcima plazme pacijenata sa atrijalnom fibrilacijom, koji su
bili hospitalizovani, pod strogim medicinskim nadzorom. Određene koncentracije su bile u
očekivanom opsegu.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Development and validation of liquid chromatography tandem mass spectrometry method for determination of rivaroxaban in plasma samples, Razvoj i validacija metode tečne hromatografije spregnute sa masenom spektrometrijom za određivanje sadržaja rivaroksabana u uzorcima plazme",
volume = "72",
number = "4 suplement",
pages = "S534-S535",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4599"
}
