高效液相色谱法测定附片（黑顺片）配方颗粒的单酯型生物碱含量及双酯型生物碱限度

doi:10.19803/j.1672-8629.20260284

中国药物警戒 ›› 2026, Vol. 23 ›› Issue (6): 643-648.
DOI: 10.19803/j.1672-8629.20260284

高效液相色谱法测定附片（黑顺片）配方颗粒的单酯型生物碱含量及双酯型生物碱限度

王敏舒¹, 程鼎^1Δ, 吴成凤^2,3, 张春艳^2,3, 杨玉琴^1#, 张治国^1,*

¹中国中医科学院中医基础理论研究所,北京 100700;
²华润三九现代中药制药有限公司,广东惠州 516000;
³华润三九医药股份有限公司,广东深圳 518110

收稿日期:2026-04-08 出版日期:2026-06-15 发布日期:2026-06-18
通讯作者: ^*张治国,男,博士,研究员,中医药研究。E-mail: zzgtcm@163.com。^#为共同通信作者。
作者简介:王敏舒,女,硕士,药效物质基础研究。^Δ为并列第一作者。
基金资助:
国家自然科学基金资助项目（82204600）; 附子及甘草附子汤不同剂型的毒性成分分析、毒效评价及生物利用度研究（XH202514）

Determination of Contents of Monoester Alkaloids and Limit Test of Diester Alkaloids in Fupian (Heishunpian) Formula Granules by HPLC

WANG Minshu¹, CHENG Ding^1Δ, WU Chengfeng^2,3, ZHANG Chunyan^2,3, YANG Yuqin^1#, ZHANG Zhiguo^1,*

¹Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China;
²China Resources Sanjiu Modern Chinese Medicine Pharmaceutical Co., Ltd., Huizhou Guangdong 516000, China;
³China Resources Sanjiu Medical & Pharmaceutical Co., Ltd., Shenzhen Guangdong 518110, China;

Received:2026-04-08 Online:2026-06-15 Published:2026-06-18

摘要/Abstract

摘要： 目的建立高效液相色谱（HPLC）法同时测定3种单酯型生物碱（苯甲酰新乌头原碱、苯甲酰乌头原碱、苯甲酰次乌头原碱）含量,并对3种双酯型生物碱（新乌头碱、乌头碱、次乌头碱）进行限度检查,为相关样品的质量控制提供新的检测途径。方法以附片（黑顺片）配方颗粒为研究对象,首先采用国家药品标准规定的高效液相色谱-三重四极杆质谱联用（HPLC-MS/MS）法确认样品符合标准规定;其次建立HPLC含量测定方法,测定样品的单酯型生物碱含量和双酯型生物碱限度;最后采用所建立的HPLC法对多批次样品进行含量测定与限度检查验证。结果 HPLC-MS/MS法测定结果显示,1 g样品中3种单酯型生物碱共1.5 mg·g^-1、3种双酯型生物碱共2.5 μg·g^-1,符合国家药品标准中要求的总量为0.4~1.5 mg·g^-1及不得过80 μg·g^-1限度要求;建立的HPLC法中,3种单酯型生物碱在测定浓度范围内线性关系良好（相关系数R²>0.999）,1 g样品中3种单酯型生物碱总量为1.3 mg·g^-1,符合国家药品标准要求,双酯型生物碱未检出,结合仪器定量限与国家药品标准限度规定（总量达到或接近限量上限可被检出）,判定双酯型生物碱总量低于国家药品标准要求的限度,符合限度要求;HPLC法验证测定中,各批次样品中单酯型生物碱符合相关标准规定,双酯型生物碱均未检出。结论建立的HPLC法操作简便、仪器普适性高,在线性范围内可实现附片（黑顺片）配方颗粒中单酯型生物碱的含量测定与双酯型生物碱的限度检查,提供一种补充检测手段。

关键词: 附片（黑顺片）配方颗粒, 单酯型生物碱, 双酯型生物碱, 高效液相色谱法, 液质联用技术, 生物碱检测

Abstract: Objective To establish a high performance liquid chromatography (HPLC) method for simultaneous determination of three monoester alkaloids and for the limit test of three diester alkaloids so as to offer a feasible detection approach to quality control of related samples. Methods Using Fupian (Heishunpian) formula granules as the subject, the contents of three monoester alkaloids and three diester alkaloids were determined by HPLC-tandem mass spectrometry (HPLC-MS/MS) before an HPLC method was established to determine the contents of the three monoester alkaloids, the limit test of diester alkaloids and those of multiple batches of samples of Fupian (Heishunpian) formula granules. Results The HPLC-MS/MS results showed that 1 g of the test sample contained a total of 1.5 mg of monoester alkaloids and a total of 2.5 μg of diester alkaloids, which met the national standard. Using the established HPLC method, the three monoester alkaloids were highly linear within the range of tested concentrations (correlation coefficient R²>0.999), The total content of monoester alkaloid in 1 g of Fupian (Heishunpian) formula granules was 1.3 mg·g^-1, and no diester alkaloids were detected. Based on the instrumental quantitation limit and the national standard limit, the contents of diester alkaloids were believed to comply with the limit requirement. In multiple batches of samples detected by HPLC, the contents of monoester alkaloids all met the related standard and no diester alkaloids were detected. Conclusion The HPLC method established in this study is user-friendly and has excellent universality. Within the linear range, it can be used for the determination of monoester alkaloids and the limit test of diester alkaloids in Fupian (Heishunpian) formula granules as a complementary detection approach.

Key words: Fupian (Heishunpian) Formula Granules, Monoester Alkaloids, Diester Alkaloids, High Performance Liquid Chromatography (HPLC) Method, Liquid Chromatography-Tandem Mass Spectrometry (LC-MS), Alkaloid Determination

中图分类号:

R282
R927

王敏舒, 程鼎, 吴成凤, 张春艳, 杨玉琴, 张治国. 高效液相色谱法测定附片（黑顺片）配方颗粒的单酯型生物碱含量及双酯型生物碱限度[J]. 中国药物警戒, 2026, 23(6): 643-648.

WANG Minshu, CHENG Ding, WU Chengfeng, ZHANG Chunyan, YANG Yuqin, ZHANG Zhiguo. Determination of Contents of Monoester Alkaloids and Limit Test of Diester Alkaloids in Fupian (Heishunpian) Formula Granules by HPLC[J]. Chinese Journal of Pharmacovigilance, 2026, 23(6): 643-648.

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https://zgywjj.magtechjournal.com/CN/Y2026/V23/I6/643

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高效液相色谱法测定附片（黑顺片）配方颗粒的单酯型生物碱含量及双酯型生物碱限度

Determination of Contents of Monoester Alkaloids and Limit Test of Diester Alkaloids in Fupian (Heishunpian) Formula Granules by HPLC

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