硫熏白芍配方颗粒检控指标的探讨

目的鉴于前期研究发现硫熏药材特征含硫衍生物比二氧化硫(SO_2)残留指标更具专属性和重现性,现探讨SO_2、芍药苷和芍药苷亚硫酸酯(硫熏特征含硫衍生物)作为硫熏白芍配方颗粒检控指标的可行性。方法采用《中国药典》2015年版SO_2残留测定法和HPLC法,考察模拟硫熏白芍配方颗粒制剂过程中(提取、浓缩和干燥)SO_2残留和芍药苷及芍药苷亚硫酸酯的量转移规律。结果在硫熏白芍提取液、浓缩液和干浸膏中均能检测到SO_2残留、芍药苷和芍药苷亚硫酸酯,说明三者均可指示硫熏白芍配方颗粒制剂过程质量变化;但三者量转移规律不同,SO_2和芍药苷呈下降趋势,最终转移率分别为25.5%和91.8%,而芍药苷亚硫酸酯呈上升趋势,最终转移率为118.5%。对市售白芍配方颗粒检测可知,全部样品中均检测到芍药苷,凡测到SO_2残留的样品,也可检测到芍药苷亚硫酸酯。结论鉴于SO_2残留是安全性指标,而芍药苷和芍药苷亚硫酸酯分别反映了白芍配方颗粒内在质量和硫熏影响程度,故三者结合可科学评价硫熏白芍配方颗粒的品质,客观表征其安全性和有效性。

Chemical markers for quality control of sulfur-fumigated Paeoniae Radix Alba dispensing granules

Objective Previous studies found that characteristic sulfur-containing derivatives induced by sulfur-fumigation of medicinal herbs could be used together with sulfur dioxide (SO₂) as chemical markers for the quality control of sulfur-fumigated herbs owing to the more specific and reproducibility of characteristic sulfur-containing derivatives over SO₂ index. In this paper, the feasibility of these two indices used for the quality control of herbal dispensing granules was further investigated. Methods Using Paeoniae Radix Alba (PRA) as an example, the contents of SO₂, paeoniflorin as well as paeoniflorin sulfonate, the characteristic sulfur-containing derivatives of sulfur-fumigated RPA in PRA processing pieces, decoctions, concentrates, and dried extracts were quantified by SO₂ residue determination method documented in Chinese Pharmacopeia and HPLC technique, and the transfer ratios of these components during preparation procedures of PRA dispensing granules were evaluated. Results It was found that SO₂, paeoniflorin and paeoniflorin sulfonate could all be detectable in the samples of decoctions, concentrates and dried extracts, indicating that these three components could be used as chemical markers to indicate the quality changes during preparation of PRA dispensing granules. However, the transfer ratios of these three components were different from each other, with the contents of SO₂ and paeoniflorin decreased, whereas that of paeoniflorin sulfonate increased during preparation of PRA dispensing granules. In addition, in those commercial PRA dispensing granules samples SO₂ detectable, paeoniflorin sulfonate also detectable. Conclusion Since SO₂ residue is a safety index, while paeoniflorin and paeoniflorin sulfonate can reflect the inner quality and the impact extent of sulfur-fumigation on the quality of PRA dispensing granules respectively, the three components might be used together as chemical markers for the quality control, and consequently to ensure the safety and efficacy of PRA dispensing granules.