High performance liquid chromatography-based quantification of aspirin, clopidogrel, and ticagrelor in plasma of patients with coronary artery disease: A comprehensive review

Cardiovascular diseases (CVD), primarily coronary artery disease (CAD), remain a leading cause of mortality globally. Analytical quantification of Clopidogrel, Ticagrelor, and Aspirin in plasma is essential for understanding their pharmacokinetics and optimizing therapeutic efficacy in managing coronary artery disease. A systematic–narrative review was conducted to assess analytical techniques used in quantifying Clopidogrel, Ticagrelor, and Aspirin in plasma samples. PubMed was searched from 1985 to 2022 using specific keywords and inclusion criteria focused on human plasma samples and indexed clinical studies in English.  A total of 61 studies have been used in this qualitative review. Methodologies predominantly employed high-performance liquid chromatography (HPLC) with varied sample preparation techniques, including liquid-liquid extraction (LLE) and protein precipitation. LLE methods using ethyl acetate, diethyl ether, and other solvents showed promising recoveries. Acetonitrile-based protein precipitation provided recovery rates of 80-85%, superior to methanol-based precipitation. but was associated with peak distortion and poor chromatographic resolution. Solid-phase extraction yielded slightly lower recovery (70–78%) but produced sharper, more reproducible peaks suitable for accurate quantification. This review demonstrates that while HPLC-based techniques with varied extraction methods remain central to quantifying Clopidogrel, Ticagrelor, and Aspirin in plasma, the lack of methodological standardization highlights the need for more consistent, validated approaches across clinical studies.  Investigating genetic influences, notably CYP2C19 genotyping, could enhance comprehension of Clopidogrel metabolism and patient responsiveness.