Clopidogrel bisulfate

Clopidogrel contains a center of dissymmetry, and hence is capable of being resolved into its two mirror image compounds. It has been found that only the (S)-enantiomer, which corresponds to the dextrorotatory form, has antithrombotic activity and that the (R)-enantiomer, which corresponds to the levorotatory form, does not exhibit antithrombotic activity. Moreover, in animal studies, the (R)-enantiomer triggered convulsions at high doses. Consequently, (R)-clopidogrel bisulfate is considered to be one of the impurities in (S)-clopidogrel bisulfate bulk drug substance. Clopidogrel is extensively metabolized in vivo by carboxylesterase hydrolysis on the ester function, resulting in the formation of clopidogrel carboxylic acid (CCA) as the inactive metabolite of clopidogrel. In addition, small amounts of clopidogrel are converted to a pharmacologically active metabolite (AM) via the intermediate metabolite inactive 2-oxoclopidogrel, which is then converted to an AM by a two-step cytochrome P450 oxidation process. Due to the instability of clopidogrel AM and the abundant availability of the more stable CCA in human plasma, CCA is used to indirectly determine the pharmacokinetics of clopidogrel. Furthermore, there is also a possibility that (S)-clopidogrel undergoes an in vivo chiral inversion into the other clopidogrel enantiomer, which becomes hydrolyzed to (R)-CCA. Metabolic pathways and potential in vivo chiral inversions of clopidogrel are described. Until recently, only chromatographic methods were used to determine clopidogrel in biological samples.