Simultaneous quantitation of acetylsalicylic acid and clopidogrel along with their metabolites in human plasma using liquid chromatography tandem mass spectrometry

Abstract

The interest in therapeutic drug monitoring has increased over the last few years. Inter- and intra-patient variability in pharmacokinetics, plasma concentration related toxicity and success of therapy have stressed the need of frequent therapeutic drug monitoring of the drugs. A sensitive, selective and rapid liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous quantification of acetylsalicylic acid (aspirin), salicylic acid, clopidogrel and carboxylic acid metabolite of clopidogrel in human plasma. The chromatographic separations were achieved on Waters Symmetry Shield(TM) C18 column (150 × 4.6 mm, 5 µm) using 3.5 mm ammonium acetate (pH 3.5)-acetonitrile (10:90, v/v) as mobile phase at a flow rate of 0.75 mL/min. The present method was successfully applied for therapeutic drug monitoring of aspirin and clopidogrel in 67 patients with coronary artery disease.

The Herb‐Drug Interaction of Clopidogrel and Xuesaitong Dispersible Tablet by Modulation of the Pharmacodynamics and Liver Carboxylesterase 1A Metabolism

“…The method was validated in terms of linearity, accuracy and precision, selectivity, matrix effect (ME), recovery, and stability according to the guidelines for bioanalytical method development recommended by the US Food and Drug Administration and related literature for CAMD detection [ 14 , 29 ].…”

“…During clopidogrel metabolism [ 11 , 12 ], carboxylesterase 1A (CES1A) begins by hydrolyzing approximately 85-90% of the prodrug to an inactive carboxylic acid metabolite [ 13 ]. A portion of the prodrug is transformed into the inactive 2-oxo-clopidogrel [ 6 ], and the remainder is oxidized to the active thiol metabolite by CYP enzymes ( Figure 1 ) [ 14 , 15 ]. Only approximately 2% of the clopidogrel dose reaches systemic circulation where it becomes available through irreversible binding to the platelet P2Y12 receptor to have an antiplatelet aggregation effect [ 16 ].…”

Development and Validation of a Method for the Simultaneous Quantification of Aspirin, Salicylic Acid, Rosuvastatin, Rosuvastatin Lactone and N-Desmethyl Rosuvastatin in Human Plasma Using UPLC-MS/MS-API-5500

“…Literature survey shows that RP-HPLC stability indicating methods for rosuvastatin alone or with combination [2], LC-MS/MS methods for plasma for rosuvastatin alone or with metabolites/combination of other drugs [3][4][5][6][7][8][9][10][11][12][13][14][15][16], LC-MS/MS methods for plasma for aspirin alone or with metabolites/combination of other drugs [17][18][19][20][21][22][23][24][25] are reported. It is noted that method for simultaneous estimation of RVT with metabolites and ASP with metabolite is not available.…”

Development and Validation of an Alternate Stability-indicating UV Spectrophotometric Analytical Method for Aspirin in Tablets

“…In addition, a literature survey exposed there were numerous analytical methodologies to detect ASP and SA in tablets and biofluids [6][7][8][9][10][11][12][13][14][15][16][17] . Particularly, for the pharmaceutical industry, the interest raises on the need of developing robust analytical stability methods to ensure drugs will not degrade until the sell-by date has expired [18,19] .…”