Cheng Dong, Zhou Ying, Li Wei, Shan Chen-Xiao, Chai Chuan, Cui Xiao-Bing, Kang Bi, Wang Tian-Lin, Wen Hong-Mei
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
J Chromatogr Sci. 2015 Sep;53(8):1280-8. doi: 10.1093/chromsci/bmu230. Epub 2015 Feb 12.
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, (1)H and (13)C 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.
采用高效液相色谱法（HPLC）对作为活性药物成分（API）的利谷甾醇二醇进行杂质分析，结果鉴定出两种相关杂质。因此，为了提高利谷甾醇二醇原料药的质量控制，我们鉴定并开发了一种通过液相色谱-飞行时间-质谱联用仪（LC-TOF-MS-MS）定量这两种杂质（杂质-1和杂质-2）的方法，然后对其进行化学合成以便进一步研究。基于红外光谱（IR）、质谱（MS）、氢核磁共振（¹H NMR）和碳核磁共振（¹³C NMR）的光谱数据，杂质-1和杂质-2的结构分别被表征为2-羟甲基-3,6-二甲基吡嗪和2-羟甲基-3,5,6-三甲基吡嗪。我们根据国际协调会议指南进一步验证了该方法，以证明所述方法的灵敏度、精密度、线性、准确度和稳定性。此外，还详细讨论了利谷甾醇二醇原料药中杂质-1和杂质-2形成的潜在机制。
