HPLC-MS/MS法同时测定中药口服液体制剂中45种添加剂

唐维英, 魏宇涛, 温泉, 徐峰, 李澍才

doi:10.16155/j.0254-1793.2024.03.16

药物分析杂志 >

2024 , Vol. 44 >Issue 3: 501 - 511

DOI: https://doi.org/10.16155/j.0254-1793.2024.03.16

安全监测

HPLC-MS/MS法同时测定中药口服液体制剂中45种添加剂

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1.四川省药品检验研究院,药物制剂体内外相关性技术研究国家药监局重点实验室,成都 611731;
2.四川省食品检验研究院,成都 611731;
3.国家市场监管重点实验室(白酒监管技术),成都 611731

第一作者 Tel:18382093778;E-mail:1016506196@qq.com

^**Tel:1832807329;E-mail:314474984@qq.com

收稿日期: 2023-08-11

网络出版日期: 2024-06-21

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Simultaneous determination of 45 additives in oral liquid preparations of traditional Chinese medicine by HPLC-MS/MS

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1. Sichuan Institute of Drug Control, NMPA Key Laboratory for Technical Research on Drug Products in Vitro and in Vivo Correlation, Chengdu 611731, China;
2. Sichuan Institute of Food Inspection, Chengdu 611731, China;
3. Key Laboratory of Baijiu Supervising Technology for State Market Regulation, Chengdu 611731, China

Received date: 2023-08-11

Online published: 2024-06-21

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摘要

目的: 建立并优化了高效液相色谱-串联质谱(HPLC-MS/MS)同时测定中药口服液体制剂中45种添加剂化合物的分析方法。方法: 样品经乙腈-甲醇(9∶1)(含0.1%甲酸)超声提取,Agilent Eclipse Plus C₁₈(150 mm×3.0 mm,1.8 μm)色谱柱进行分离,以甲醇和5 mmol·L^-1乙酸铵为流动相梯度洗脱,采用电喷雾离子源正、负离子同时扫描,动态多反应监测模式,保留时间和离子丰度比进行定性分析以及外标法定量。结果: 在优化的色谱-质谱条件下,45种添加剂化合物在5~2 000 ng·mL^-1范围内线性良好(r≥0.992);方法定量限为0.2~4.0 mg·kg^-1;各待测物在空白样品中不同加标水平下的平均回收率为75.4%~118.4%;RSD为0.70%~9.8%。应用该方法对从药房购买的20批中药口服液体制剂样品进行检测,其中6批次样品检出苯甲酸,含量为0.13%~0.27%,7批次样品分别检出山梨酸、肉桂酸、甜蜜素、4-羟基苯甲酸乙酯、安赛蜜、脱氢乙酸和糖精钠。结论: 建立的高通量检测方法灵敏、前处理简便、快速、准确度高、回收率稳定,能有效降低检测成本,可用于中药口服液体制剂中多种添加剂化合物的同时快速筛查。

关键词： 添加剂; 中药口服液体制剂; 高效液相色谱-串联质谱; 高通量; 动态多反应监测

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唐维英, 魏宇涛, 温泉, 徐峰, 李澍才 . HPLC-MS/MS法同时测定中药口服液体制剂中45种添加剂[J]. 药物分析杂志, 2024 , 44(3) : 501 -511 . DOI: 10.16155/j.0254-1793.2024.03.16

Abstract

Objective: To establish an high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the simultaneous determination of 45 additives in oral liquid preparations of traditional Chinese medicine. Methods: The samples were ultrasonically extracted by acetonitrile-methanol (9∶1) (containing 0.1% formic acid). The separation was carried out on an Agilent Eclipse Plus C₁₈ chromatographic column (150 mm×3.0 mm,1.8μm) using gradient elution of methanol -5 mmol·L^-1 ammonium acetate. The compounds were scanned and detected simultaneously by electrospray ionization(ESI)ion source in both positive ion and negative ion mode under dynamic multiple reaction monitoring. The retention time and ion ratio were used for qualitative analysis and the external standard method was adopted for quantification. Results: The good linear relationship of peak area was observed for the 45 additives with correlation coefficients ≥0.992 in the concentration range of 5-2 000 ng·mL^-1, and the limits of quantitation were between 0.2 mg·kg^-1 and 4.0 mg·kg^-1 under the above chromatographic and mass spectrometric conditions. The average recoveries of the blank samples at different added levels ranged from 75.4% to 118.4% with RSDs of 0.70%-9.8%. The method was used to detect 20 batches of oral liquid preparations of traditional Chinese medicines purchased from pharmacies. Benzoic acid was detected in 6 batches with the contents of benzoic acid from 0.13% to 0.27%, and sorbic acid, trans-cinnamic acid, molasses, ethyl 4-hydroxybenzoate, acesulfame potassium, dehydroacetic acid and saccharin sodium were detected in 7 batches of samples respectively. Conclusion: The established high-throughput detection method is sensitive, simple and fast in pre-treatment, with high accuracy, stable recovery and reduced detection cost effectively. It can be used for the simultaneous rapid screening of multiple additives in oral liquid preparations of traditional Chinese medicine.

Key words： additives; oral liquid preparations of traditional Chinese medicine; ultra-high performance liquid chromatography tandem mass spectrometry; high throughput; dynamic multiple reaction monitoring

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