左亚叶酸钠原料药中两个主要杂质结构的研究

Structural identification of two major impurities in sodium levofolinate

为了分离制备左亚叶酸钠原料药中两个主要杂质,并对其进行结构鉴定,建立了新的色谱系统,色谱柱为Lichrospher C18柱,流动相为乙腈-0.5%甲酸溶液(5∶95),检测波长为280 nm。利用该色谱系统将两个杂质制备出来,并对其进行LC-Q-TOF及LC-MS/MS的检测,获得两个杂质准确的相对分子质量、分子式组成及一级和二级质谱,并对准分子离子的各个产物离子进行归属,推测了两个主要杂质可能的化学结构。杂质1和杂质2的化学结构分别被鉴定为7-羟基-8-氢叶酸和10-甲酰叶酸,其中7-羟基-8-氢叶酸的结构未见文献报道。本研究所建立的方法有效地鉴定了左亚叶酸钠原料药中两个主要杂质可能的化学结构,为其质量控制提供了理论依据。

A novel HPLC method was established, which was carried out on a Lichrospher C18 column with a mobile phase consisting of aeetonitrile - O. 5% formic acid aqueous solution （5： 95） and a detection wavelength of 280 nm. Two major impurities in bulk material of sodium levofolinate were prepared by this method. Their exact molecular weights were acquired by LC-Q-TOF. Their full scan mass spectra and product ion scan mass spectra were obtained by LC-MS/MS. The fragment profiles of two target impurities were explained and their chemical structures were elucidated. Impurity 1 was identified as 7-hydroxy-8-hydrofolie acid in sodium levofolinate bulk material for the first time. Impurity 2 was identified as lO-formylfolic acid. This method is effective in identifying two major impurities in bulk material of sodium tevofolinate are useful for its quality eontroll. detected by the current HPLC method, and the results