HPLC method for simultaneous analysis of ticagrelor and its organic impurities and identification of two major photodegradation products.
A simple, fast and sensitive analytical method by high-performance liquid chromatography (HPLC) was developed and validated for the simultaneous determination of ticagrelor and two synthesis impurities. The HPLC method was established using an Agilent 1200 Series equipment coupled to photodiode array detector (PDA) at 270nm with a Zorbax Plus C8column (150×4.6mm, 5.0μm), injection volume of 20μL, and a constant temperature of 25°C. The mobile phase consisted of acetonitrile: ammonium acetate 50mM (57:43, v/v) and pH adjusted to 8.2 with ammonium hydroxide 6M, at a flow rate of 0.7mL/min. No interference peaks from excipients and diluent system indicated the specificity of the method. The calibration curves showed determination coefficients (r2)>0.99, calculated by linear regression. The limit of quantitation (LOQ) for impurities 1 and 2 were 2.0 and 0.2μg/mL, respectively. Intra and interday relative standard deviations (RSDs) were <2% for ticagrelor and <6% for the impurities, proving the precision of the method. Besides, two mayor degradation products formed when sample solutions of ticagrelor were exposed to UVC radiation were elucidated and the mechanisms involved in the photolytic degradation of ticagrelor were proposed.
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, Porto Alegre, RS, Brazil. Electronic address: maronesi@yahoo.com.br.
Lívia Maronesi
LM
Bueno
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, Porto Alegre, RS, Brazil.
Joanna Wittckind
JW
Manoel
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, Porto Alegre, RS, Brazil.
Camila Ferrazza Alves
CF
Giordani
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, Porto Alegre, RS, Brazil.
Andreas Sebastian Loureiro
AS
Mendez
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, Porto Alegre, RS, Brazil.
Nadia Maria
NM
Volpato
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, Porto Alegre, RS, Brazil.
Elfrides Eva Scherman
EE
Schapoval
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, Porto Alegre, RS, Brazil.
Martin
M
Steppe
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, Porto Alegre, RS, Brazil.
Cássia Virginia
CV
Garcia
D000241:Adenosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry; D002623:Chemistry Techniques, Analytical / Q000379:methods* / Q000592:standards; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000592:standards; D004340:Drug Contamination; D010782:Photolysis; D000077486:Ticagrelor
D000077486:Ticagrelor; D000241:Adenosine
Degradation products; Drug impurities; HPLC; Ticagrelor; Validation