Development of an LC-MS/MS method for simultaneous determination of ticagrelor and its active metabolite during concomitant treatment with atorvastatin.
J Chromatogr B Analyt Technol Biomed Life Sci
; 1105: 113-119, 2019 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-30580183
ABSTRACT
A combination of antiplatelet drugs with high-intensity statin therapy is a standard in patients with coronary events. Concomitant treatment with ticagrelor, a moderate CYP3A4 inhibitor, and CYP3A4-metabolized statins such as atorvastatin, might lead to an increased risk of muscle-related adverse events. Therefore, investigation of concentrations of these compounds in clinical samples is necessary. For this purpose, an LC-MS/MS method was developed for simultaneous determination of ticagrelor and its active metabolite (AR-C124910XX), as well as 2-hydroxyatorvastatin, which is the main metabolite of atorvastatin. Protein precipitation was used for sample preparation and afterwards the analytes were separated on a Kinetex XB-C18 column with an isocratic elution (water and acetonitrile with 0.1% formic acid, 5743, v/v). Detection was performed on a triple-quadrupole MS with multiple-reaction-monitoring via electrospray ionization. The method was fully validated according to the EMA's recommendations. Determination was possible within ranges 1.25-2000â¯ng/mL for ticagrelor, 1.25-1000â¯ng/mL for its AR-C124910XX, 1.25-50â¯ng/mL for atorvastatin and 1.14-45.73 for 2-hydroxyatorvastatin. Within and between-run accuracy, expressed as a relative error, was within 0.05-10.56% for all analytes, while within and between-run precision, expressed as coefficient of variation, was within 0.61-9.91%. Ticagrelor, atorvastatin and their main metabolites were found to be stable in acetonitrile stock solutions, and in plasma samples stored for 24â¯h at room temperature, 1â¯month at -25⯰C, after 3â¯cycles of freezing and thawing, and in processed samples stored as a dry residue for 24â¯h at 4⯰C and for 24â¯h in autosampler at room temperature. This simple and rapid method allowed simultaneous determination of the analytes for the first time. The procedure was applied for the pharmacokinetic study of ticagrelor, its active metabolite AR-C124910XX, and 2-hydroxyatorvastatin in patients simultaneously treated with ticagrelor and atorvastatin.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Inibidores da Agregação Plaquetária
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Cromatografia Líquida
/
Espectrometria de Massas em Tandem
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Ticagrelor
Tipo de estudo:
Guideline
/
Prognostic_studies
Limite:
Humans
/
Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article