含千里光中药制剂中肝毒性成分阿多尼弗林碱的含量分析

Quantification of hepatotoxic pyrrolizidine alkaloid adonifoline in traditional Chinese medicine preparations containing Senecionis Scandentis Herba

吡咯里西啶生物碱(PAs)是一种天然毒性物质,可导致显著的肝毒性、肺脏毒性、遗传毒性、神经毒性和胚胎毒性等,甚至死亡。因此含PAs的中草药及制剂一直是世界卫生组织等国际组织及国家严密监控的对象。PAs广泛存在于我国多种药用植物中,涉及中药成方制剂数百种。《中国药典》2015年版明确规定了千里光药材中阿多尼弗林碱的限量,但对含有该药材的制剂并未做任何规定,对其他数十种相关制剂中阿多尼弗林碱的限量也未做规定。该研究收集了包括《中国药典》收录的千柏鼻炎片、千柏鼻炎胶囊等常用的14种含千里光的中药制剂,并采用UPLC-MS技术检测了阿多尼弗林碱的含量。结果在8种制剂中均检测到了阿多尼弗林碱,包括千柏鼻炎片、千柏鼻炎胶囊等,其平均含量远高于德国、荷兰和新西兰的相关标准。且同一复方不同批次间含量差异较大,最高质量分数为156.10μg·g-1,按该批制剂推荐用量每日摄入阿多尼弗林碱最高达1030.26μg,提示服用含千里光的制剂需注意其用药安全,对复方中千里光药材含量较高的制剂尤其应该注意阿多尼弗林碱的限量检查。

Pyrrolizidine alkaloids(PAs)are a kind of natural toxins,which can cause severe hepatotoxicity,pulmonary toxicity,genotoxicity,neurotoxicity,embryotoxicity and even death.Therefore,international organizations and countries such as World Health Organization have paid great attention to herbal medicines and preparations containing PAs.PAs are widely distributed in Chinese herb medicines and contained in hundreds of traditional Chinese medicine preparations.The content of adonifoline,the main PAs in Senecionis Scandentis Herba,shall be less than 0.004%in herbal medicines as described in Chinese pharmacopeia.However,there is no guidance in preparations which contain Senecionis Scandentis Herba.In this study,14 preparations were analyzed by an UPLC-MS method.Among them,8 preparations were found to contain adonifoline much higher than the content limits of such countries as Germany,Netherlands and New Zealand.And the highest contents of adonifoline were found in Qianbai Biyan Tablets and Qianbai Biyan Capsules,which are officially recorded in Chinese Pharmacopeia.The contents of adonifoline varied in different batches of the same preparations.The highest content was 156.10μg·g-1 Qianbai Biyan Tablets,whose daily intake of adonifoline was up to 1030.26μg according to the recommended dosage of the preparation.Our results showed the potential risk of these preparations,and the content limit of adonifoline shall be inspected Chinese medicine preparations containing Senecionis Scandentis Herba.