Journal article
Liquid Chromatography-Tandem Mass Spectrometry Method for Ticagrelor and its Active Metabolite Determination in Human Plasma: Application to a Pharmacokinetic Study
- Marsousi, Niloufar School of Pharmaceutical sciences, Geneva University, Geneva, Switzerland
- Rudaz, Serge School of Pharmaceutical sciences, Geneva University, Geneva, Switzerland
- Desmeules, Jules A. School of Pharmaceutical sciences, Geneva University, Geneva, Switzerland
- Daali, Youssef School of Pharmaceutical sciences, Geneva University, Geneva, Switzerland
Published in:
- Current Analytical Chemistry. - Bentham Science Publishers Ltd.. - 2020, vol. 16, no. 5, p. 602-608
English
Background:
Ticagrelor is a highly recommended new antiplatelet agent for the treatment
of patients with acute coronary syndrome at moderate or high ischemic risk. There is a real need for
rapid and accurate analytical methods for ticagrelor determination in biological fluids for pharmacokinetic
studies. In this study, a sensitive and specific LC-MS method was developed and validated
for quantification of ticagrelor and its Active Metabolite (AM) in human plasma over expected clinical
concentrations.
Methods:
Samples were handled by Liquid-Liquid Extraction (LLE). A linear gradient was applied
with a mobile phase composed of formic acid 0.1% and acetonitrile with 0.1% of formic acid using a
C18 reversed-phase column. MS spectra were obtained by electrospray ionization in negative mode
and optimized at 521.4→360.9 m/z, 477.2→361.2 m/z and 528.1→367.9 m/z transitions for ticagrelor,
AM and ticagrelor-d7, respectively.
Results:
This method allowed rapid elution, in less than 4 minutes, and quantification of concentrations
as low as 2 ng/mL for ticagrelor and 1 ng/mL for AM using only 100 μL of human plasma.
LLE using hexane/ethyl acetate (50/50) was an optimal compromise in terms of extraction recovery
and endogenous compounds interference. Trueness values of 87.8% and 89.5% and precisions of
84.1% and 93.8% were obtained for ticagrelor and AM, respectively. Finally, the usefulness of the
method was assessed in a clinical trial where a single 180 mg ticagrelor was orally administered to
healthy male volunteers. Pharmacokinetic parameters of ticagrelor and its active metabolite were
successfully determined.
Conclusion:
A sensitive and specific quantification LC-MS-MS method was developed and validated
for ticagrelor and its active metabolite determination in human plasma. The method was successfully
applied to a clinical trial where a single ticagrelor 180 mg dose was orally administered to
healthy male volunteers. The described method allows quantification of concentrations as low as 2
ng/mL of ticagrelor and 1 ng/mL of the metabolite using only 100 μL of plasma.
of patients with acute coronary syndrome at moderate or high ischemic risk. There is a real need for
rapid and accurate analytical methods for ticagrelor determination in biological fluids for pharmacokinetic
studies. In this study, a sensitive and specific LC-MS method was developed and validated
for quantification of ticagrelor and its Active Metabolite (AM) in human plasma over expected clinical
concentrations.
with a mobile phase composed of formic acid 0.1% and acetonitrile with 0.1% of formic acid using a
C18 reversed-phase column. MS spectra were obtained by electrospray ionization in negative mode
and optimized at 521.4→360.9 m/z, 477.2→361.2 m/z and 528.1→367.9 m/z transitions for ticagrelor,
AM and ticagrelor-d7, respectively.
as low as 2 ng/mL for ticagrelor and 1 ng/mL for AM using only 100 μL of human plasma.
LLE using hexane/ethyl acetate (50/50) was an optimal compromise in terms of extraction recovery
and endogenous compounds interference. Trueness values of 87.8% and 89.5% and precisions of
84.1% and 93.8% were obtained for ticagrelor and AM, respectively. Finally, the usefulness of the
method was assessed in a clinical trial where a single 180 mg ticagrelor was orally administered to
healthy male volunteers. Pharmacokinetic parameters of ticagrelor and its active metabolite were
successfully determined.
for ticagrelor and its active metabolite determination in human plasma. The method was successfully
applied to a clinical trial where a single ticagrelor 180 mg dose was orally administered to
healthy male volunteers. The described method allows quantification of concentrations as low as 2
ng/mL of ticagrelor and 1 ng/mL of the metabolite using only 100 μL of plasma.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.2174/1573411015666190220144904
- ISSN 1573-4110
- Persistent URL
- https://sonar.ch/global/documents/252220
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