Identification, Characterization, Synthesis and Quantification of Related Impurities of Liguzinediol

摘要

An HPLC method was employed to create an impurity profile for liguzinediol as an active pharmaceutical ingredient (API), which resulted in the identification of two related impurities. Therefore, in order to improve the quality control of the liguzinediol-API, we identified and then developed a method for quantifying the two impurities (impurity-1 and impurity-2) by LC-TOF-MS-MS and then chemically synthesized them for further studies. Based on spectral data from IR, MS, H-1 and C-13 NMR, the structures of impurity-1 and impurity-2 were characterized as 2-hydroxymethyl-3,6-dimethylpyrazine and 2-hydroxymethyl- 3,5,6-trimethylpyrazine, respectively. We further validated the method according to the International Conference on Harmonization guidelines to demonstrate the sensitivity, precision, linearity, accuracy and stability of the method described. In addition, the potential mechanisms underlying formation of impurity-1 and impurity-2 in the liguzinediol-API are discussed in detail.