Degradation kinetics and characterization of degradation products of losartan potassium by lc-ms/ms method

Abstract

U ovom radu opisano je ispitivanje stabilnosti losartan kalijuma primenom tečne hromatografije sa UV i MS-MS detekcijom i prikazan je njegov profil degradacionih proizvoda. Rastvor losartan kalijuma bio je izložen dejstvu sledećih stres agenasa: 0,1 M HCl; 0,1 M NaOH i 3% (v/v) H2O2. Rastvori losartan kalijuma analizirani su gradijentnim eluiranjem sa acetonitrilom i 0,1% (v/v) vodenim rastvorom CF3COOH pri konstantnom protoku od 0,5 ml min-1 i vremenom trajanja od 22 min. Degradacija u rastvorima losartan kalijuma koji su 7 dana bili izloženi dejstvu 0,1 M HCl i 0,1 M NaOH bila je manja od 1%, dok je u prisustvu 3% (v/v) H2O2 bila značajno veća (oko 10%). Identifikacija i strukturna analiza glavnih degradacionih proizvoda losartan kalijuma izvršena je primenom LC-MS/MS metode. Grafička zavisnost izmerenih koncentracija u funkciji vremena ukazuje da se losartan kalijum u rastvoru 3% (v/v) H2O2 degradira kinetikom pseudo nultog reda sa konstantnom brzine reakcije od 1.48ꞏ10-8 mol L-1 dan-1.

This paper presents study of losartan potassium stability evaluation by liquid chromatography with UV/VIS and MS-MS detection and its degradation profile. A solution of losartan potassium was exposed to the following stress agents: 0.1 M HCl, 0.1 M NaOH, and 3% (v/v) H2O2. The analyses of losartan potassium solutions were carried out in a gradient elution mode with acetonitrile and 0.1% (v/v) CF3COOH aqueous solution and constant flow rate of 0.5 mL min-1 within 22 min run time. After 7 days of losartan potassium solutions exposure to the stress agents at room temperature, it was found that the degree of degradation in the presence of 0.1 M HCl and 0.1 M NaOH was less than 1%, while in the presence of 3% H2O2 degradation was significantly higher (about 10%). Chemical structure elucidation of the major degradation products of losartan potassium was performed using LC-MS/MS method. The concentration versus time plot indicated that in 3% (v/v) H2O2 solution losartan potassium was degraded according to the pseudo zero-order reaction kinetics with 1.4810-8 mol L-1 day-1 rate constant. © 2019, Pharmaceutical Association of Serbia. All rights reserved.