目的 探究地龙药材至制剂过程中总砷及砷形态、价态的传递规律，以期建立地龙药材及散寒化湿颗粒（Sanhan Huashi Granules，SHG）中砷含量的限度，保障SHG的安全。方法 采用电感耦合等离子体质谱法（inductively coupledplasma mass spectrometry，ICP-MS）对经微波消解后的地龙药材到SHG进行总砷含量的测定；采用高效液相色谱-电感耦合等离子体质谱法（high performance liquid chromatography–inductively coupled plasma mass spectrometry，HPLC-ICP-MS）对其进行砷形态、价态的测定分析；并考察多批次SHG、不同产地地龙药材中砷总量以及各形态、价态的差异。结果 地龙药材、饮片、提取液及制剂在传递过程中总砷含量呈递减趋势，阴性样品中检出极少量的砷，总砷从药材至制剂的平均转移率为52.00%，饮片到制剂中的平均转移率为60.81%；28批SHG与24批地龙中砷形态及价态存在形式及规律基本一致，即基本以毒性较大的As(Ⅲ)和As(Ⅴ)为主，其他毒性较小的有机砷含量极低甚至未检出；结合地龙药材市场供应情况、多批次地龙研究结果以及临床批制剂所用地龙的使用情况，暂拟定地龙药材中As的限度为15.00 mg/kg。基于量-值传递规律及制剂处方，暂拟定SHG中As的限度为2.50 mg/kg。结论 建立的SHG中的总砷与砷形态的含量测定方法高效快速、准确性及稳定性良好。同时基于该方法初步探究了SHG中总砷及砷形态、价态的传递规律，并分别拟定地龙及SHG中砷含量的限度，为SHG的安全性及质量可控奠定基础，也为其他动物药的安全性评价与新药的研发提供参考。

Objective To investigate the transmission pattern of total arsenic, as well as the morphology and valence of arsenic, in Dilong (Pheretima) herbs and its prescription preparation, Sanhan Huashi Granules (SHG), in order to establish limits on the arsenic content in Pheretima herbs and SHG that ensure the safety of SHG. Methods Firstly, inductively coupledplasma mass spectrometry (ICP-MS) was used to determine the total arsenic content of the microwave-ablated Pheretima herbs to SHG; then HPLC-ICP-MS was employed for determining the morphology and valence of arsenic, as well as investigating the total amount, morphology, and valence differences in SHG and Pheretima herbs from different origins. Results The total arsenic content in the herbs, tablets, extracts and preparations of Pheretima in the transfer process was decreased. A very small amount of arsenic was detected in the negative samples, the average transfer rate of total As from herbs to preparations was 52.00% and the average transfer rate from decoction pieces to preparation was 60.81%. In terms of arsenic morphology and valence, there is basically no difference between 28 batches of SHG and 24 batches of Pheretima; Both mainly consist of larger toxic forms such as As(Ⅲ) and As(Ⅴ), while other organic forms have very low or undetectable toxicity levels. Considering the market supply of Pheretima herbs, multiple batch studies on Pheretima, and its use in clinical preparation batches, a tentative limit for As in Pheretima herbs is proposed at 15.00 mg/kg. Based on the pattern of volume-value transmission law and prescription requirements for preparation usage, a tentative limit for As in SHG is proposed at 2.50 mg/kg. Conclusion In this study, the method for the determination of total arsenic and arsenic form in SHG was established with high efficiency, rapidity, good accuracy and stability. Based on the method, the transfer law of total arsenic and arsenic form and valence in SHG was initially investigated to formulate the limits of elemental arsenic content in Pheretima and SHG, which will lay a foundation for the safety and quality control of SHG, and also provide a reference for the safety evaluation of other animal medicines and the research and development of new medicines.

国家重点研发计划“公共安全风险防控与应急技术装备”重点专项—散寒化湿颗粒治疗新冠肺炎的新药创制示范研究（2022YFC0868300）