Synthesis, Characterization and Development of HPLC Method for Clopidogrel Metabolite: Computational Approaches for PKPD and Toxicity Predictions

Author: Pathade P.A., Kaushik A. and Pawar A.Y.

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Abstract

The current research work emphases on synthesis, characterization, and optimization of RP-HPLC method for determination of clopidogrel and its synthesized metabolite 2-oxo-clopidogrel as an impurity simultaneously. Also the subsequent part of the paper is, ADME and toxicity of the 2-oxo-clopidogrel were predicted through different ADME database like SWISS ADME and molesoft. The metabolite 2-oxo-clopidogrel was synthesized in the laboratory and characterized by UV, IR GC/MS, NMR spectroscopy. The method was developed using Kinetex C18, 4.6 mm x 250 mm, 5 µm as stationary phase, mobile phase comprising of acetonitrile (80%): Phosphate buffer 20mM pH 3 (20%) with flow rate 1.0 mL/min, volume 20 µL through a run time of 10 minutes. The developed RP-HPLC method underwent validation based on ICH guidelines, demonstrating accuracy, precision, reproducibility, specificity, and robustness. Assessment of toxicity by using computational tools like Swiss tool is reported with the hope of reducing threats.

Keywords

Clopidogrel, 2-oxo-clopidogrel, RP-HPLC, SWISS ADME and molesoft

Conclusion

The developed HPLC method is characterized by its simplicity, accuracy, precision, sensitivity, and selectivity for the estimation of clopidogrel and its metabolite, 2-oxo-clopidogrel, which was synthesized and characterized in the laboratory. This method can also be applied to quantify 2-oxo-clopidogrel as an impurity often found in bulk drugs and formulations of clopidogrel. Moreover, there is a possibility to further optimize the method to enable the accurate quantification of 2-oxo-clopidogrel in biological fluids. This optimization would make the method highly valuable for conducting clinical and bioequivalence studies. To ensure safety, computational tools such as Swiss tool have been utilized to assess the compound's toxicity. The objective is to minimize any potential risks associated with the compound through thorough evaluation.

References

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How to cite this article

Pathade P.A., Kaushik A. and Pawar A.Y. (2023). Synthesis, Characterization and Development of HPLC Method for Clopidogrel Metabolite: Computational Approaches for PKPD and Toxicity Predictions. Biological Forum – An International Journal, 15(3): 759-770.