硫熏当归配方颗粒的安全性检控指标分析

Chemical Markers for Safety Control of Sulfur-fumigated Angelicae Sinensis Radix Dispensing Granules

目的：探讨SO_2残留和藁本内酯含硫衍生物含量作为硫熏当归配方颗粒安全性检控指标的可行性。方法：采用2015年版《中国药典》（四部）通则2331测定SO_2残留量,采用HPLC-MS/MS半定量检测藁本内酯含硫衍生物的含量,考察当归配方颗粒制剂过程（提取、浓缩和干燥）中SO_2残留和藁本内酯含硫衍生物的含量转移规律。结果：在硫熏当归提取液、浓缩液和干浸膏中均能检测到SO_2残留和藁本内酯含硫衍生物,二者在干浸膏中的最终转移率分别为8.13%和60.75%。藁本内酯含硫衍生物在配方颗粒制剂过程中的稳定性及检测方法的专属性和灵敏度均好于SO_2残留。结论：鉴于SO_2公认的有害性和藁本内酯含硫衍生物潜在的毒性,可以考虑将藁本内酯含硫衍生物结合SO_2残留作为硫熏当归配方颗粒的安全性检控指标。

Objective： To evaluate the feasibility of residual SO_2 and sulfite-ligustilide used for the safety control of herbal dispensing granules that contained sulfur-fumigated Angelicae Sinensis Radix. Method： Residual SO_2 was determined by the method documented in the 2015 edition of Chinese Pharmacopoeia, while sulfiteligustilide was analyzed semi-quantitatively by HPLC-MS/MS. The mimic Angelicae Sinensis Radix dispensing granules were self-made,and the content transfer rules of residual SO_2 and sulfite-ligustilide in sulfur-fumigated Angelicae Sinensis Radix during preparation procedures of dispensing granules,including extraction,concentration and drying,were systematically investigated. Result： Residual SO_2 and sulfite-ligustilide could all be detectable in the samples of extract,concentrate and dry extract,their final transfer ratios in dry extract were 8. 13% and60. 75%,respectively. In addition, the stability of sulfite-ligustilide in the preparation procedures of the dispensing granules and the specificity, sensitivity of the detection method were all better than residual SO_2. Conclusion： As the well-recognized harmfulness of SO_2 and potential toxicity of sulfite-ligustilide, it is suggested that sulfite-ligustilide combined with residual SO_2 could be used as indicators for the safety control of sulfur-fumigated Angelicae Sinensis Radix dispensing granules.