汤剂是中药临床最常使用的剂型之一,汤剂中化学成分的稳定性关乎临床药效与安全性。有关汤剂用水中的金属离子对中药成分稳定性影响的研究报道较少,汤剂用水是否要控制金属离子也缺少科学依据。本文以何首乌中主要成分二苯乙烯苷(2,3,5,4'-tetrahydroxy stilbene-2-O-β-D-glucoside,THSG)为例,比较研究了普通自来水、去离子水以及含不同浓度金属离子水对THSG稳定性影响的规律。结果表明,室温避光存放10天后,去离子水中THSG降解7%,而自来水中THSG完全降解;不同种类金属离子溶液均可使THSG含量下降,且下降程度与离子浓度呈浓度依赖关系。同一浓度下,Fe^3+和Fe^2+对THSG稳定性影响最大,其中500 ppm(1 ppm=1×10^-6 g·mL^-1)浓度Fe^3+和Fe^2+水溶液中THSG含量下降超过98%;通过超高效液相高分辨质谱联用仪分析,在自来水以及含Cu^2+、Ca^2+、Zn^2+、Mg^2+和Al^3+的水中发现THSG主要降解产物的可能结构为对羟基苯甲醛(相对分子质量122.036 7)和2,3,5-三羟基苯甲醛-2-O-葡萄糖苷(相对分子质量316.079 4);在含Fe^3+和Fe^2+的水中还发现可能为THSG加水二聚物的产物。上述结果表明,水中金属离子会显著影响THSG在水中的稳定性,提示如果水中金属离子不加以控制,则会对汤剂及含THSG液体制剂的临床疗效和安全性产生较大影响。临床煎制含何首乌的汤剂应使用去离子水,从而可避免在保存过程中其主要成分THSG的降解。同时,使用自来水煎制的汤剂应在短时间内服用。研究结果对加强金属离子对其他含不稳定基团(如羟基、不饱和键等)化学成分的中药汤剂稳定性的研究提供了重要信息和参考。
Decoction is one of the most commonly used dosage forms of traditional Chinese medicine. The stability of chemical constituents in decoction is closely related to the clinical efficacy and safety. There were few reports about the influence of metal ions in the stability of chemical constituents in traditional Chinese medicine. However, there is no evidence that metal ions in decoction water need to be controlled. In this study, 2,3,5,4'-tetrahydroxy stilbene-2-O-β-D-glucoside(THSG), one of the main constituents in Polygoni Multiflori Radix was studied. Ordinary tap water, deionized water, and water containing different metal ions were used to investigate and compare the influence on THSG. The results showed that after storage in a dark place at the room temperature for 10 days, the degradation of THSG was 7% in deionized water, while undetectable in tap water. The content of THSG could be decreased by different kinds of metal ions, and the effect was concentration- dependent. Moreover, Fe^3+ and Fe^2+ showed the greatest influence at the same concentration; and our study has shown that THSG decreased more than 98% in Fe^3+ and Fe^2+ solutions at 500 ppm concentration. In the same time we found out p-hydroxybenzaldehyde(molecular weight: 122.036 7) and 2,3,5-trihydroxybenzaldehyde-2- O-glycoside(molecular weight: 316.079 4) were the main degradation products of THSG in tap water and water containing Cu^2+, Ca^2+, Zn^2+, Mg^2+ and Al^3+. The product of THSG dimer with a water molecule was found in water containing Fe^3+ and Fe^2+. The above results showed that the metal ions in water could significantly influence the stability of THSG in water, indicating that the clinical efficacy and safety of decoction would be affected if the metal ions in water were not under control. It's suggested that deionized water should be used in the preparation of decoction containing Polygoni Multiflori Radix in the clinic to avoid degradation of THSG. Meanwhile, decoction prepared by tap wa