A pharmacokinetics interaction study of antiplatelet agents aspirin and clopidogrel combined with dl‐3‐n‐butylphthalide in rats by liquid chromatography–tandem mass spectrometry

A sensitive and specific high-performance liquid chromatography-tandem mass spectrometry method has been developed to determine the pharmacokinetic interactions of the antiplatelet agents aspirin and clopidogrel combined with dl-3-n-butylphthalide. For the determination of aspirin metabolite salicylic acid, clopidogrel inactive metabolite SR26334 and NBP prototype drug in rat plasma, plasma samples were prepared by precipitation of proteins using methanol containing 0.1% formic acid, followed by centrifugation. Chromatography was performed on a C18 column, eluting with a gradient of acetonitrile (with 0.1% formic acid)-water (with 0.1% formic acid). The detection adopted electrospray ion source and positive ion multiple reaction monitoring modes. The linear detection response range of salicylic acid is 80-80,000 ng/ml, and the linear detection response range of SR26334 and dl-3-n-butylphthalide is 10-10,000 ng/ml. Our study revealed that dl-3-n-butylphthalide affected the pharmacokinetics of aspirin and clopidogrel when administered to rats.