Background: Ticagrelor is a reversibly binding oral P2Y12 receptor antagonist used clinically
for the prevention of thrombotic events. A selective, rapid, and reliable method based on highperformance
liquid chromatography–tandem mass spectrometry was developed and validated for the
quantification of ticagrelor and its active metabolite AR-C124910XX in human plasma.
Method: After liquid–liquid extraction with methyl tert-butyl ether, ticagrelor and its metabolite ARC124910XX
were chromatographed on a C18 column with a mobile phase consisting of acetonitrile–
water containing 10 mM ammonium acetate (60:40, volume [v]/v) at a flow rate of 0.30 mL/min. Detection
was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring
and with a positive electrospray ionization interface using [M+H]+ ions with the following transitions:
m/z 522.9 → m/z 152.9 for ticagrelor, m/z 478.9 → m/z 152.9 for AR-C124910XX, and m/z 530.2 →
m/z 152.9 for the internal standard.
Results: Calibration curves were established in the range 4.019–2017 ng/mL for ticagrelor and 2.889–
1040 ng/mL for AR-C124910XX. The lower limits of quantification for ticagrelor and AR-C124910XX
were determined to be 4.019 and 2.889 ng/mL, respectively.
Conclusion: The method was fully validated and successfully applied to determine ticagrelor and ARC124910XX
simultaneously in human plasma and proved to be suitable for pharmacokinetic study of
ticagrelor in healthy Chinese male volunteers.