SYNTHESIS OF RIFAMPICIN IMPURITIES A AND B

Tien Dung Nguyen1, Minh Hoang Phan1, Tan Phat Huynh1, Hien Luong Thai1, Ho Nam Phan Van1,
1 Ho Chi Minh City University of Medicine and Pharmacy

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Abstract

Objectives: To synthesize impurity A (rifampicin quinone) and impurity B (rifampicin N-oxide) of rifampicin with high purity, suitable for use as reference materials. Methods: Impurity A and B were synthesized using oxidizing rifampicin with different oxidizing agents and purified using solid-phase extraction (impurity A) or flash column chromatography (impurity B). The purified products were structurally confirmed using spectroscopic techniques, including IR, MS, and NMR. Results: A total of 1,600mg of impurity A and 466.5mg of impurity B were synthesized with high purity, with yields of 56.46% and 16.10%, respectively. Conclusion: Impurity A and B of rifampicin were successfully synthesized, providing materials for establishing rifampicin impurity reference standards and contributing to the development of a national impurity reference database for quality control of related substances in drug products.

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References

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