Rapid and accurate verification of drug identity, purity and quality by 1H-NMR using similarity calculations and differential NMR
Rapid and accurate verification of drug identity, purity and quality by 1H-NMR using similarity calculations and differential NMR
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DOI：
10.1016/j.jpba.2021.114040
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发表时间：
2021-04-06
影响因子：
3.4
通讯作者：
Schripsema, Jan
中科院分区：
文献类型：
--
作者：
dos Santos Ribeiro, Helen Sant'Ana;Dagnino, Denise;Schripsema, Jan
假冒伪劣药品的非法贸易是一个价值数十亿美元的全球产业，不仅造成巨大的经济损失，而且通过直接毒性、治疗失败和抗生素耐药性的增加，给普通民众带来健康问题。需要对可疑药物进行高通量检测的技术来应对这一问题的挑战。在这项研究中，我们表明，通过核磁共振波谱 (NMR)，可以在几分钟内验证药物合规性，提供有关药物身份、纯度和质量的数据，而无需开发特定方法并使用氘化溶剂直接萃取。相似性计算和微分核磁共振波谱有助于数据的评估。通过对盐酸舍曲林、阿普唑仑、维生素 D-3、马来酸依那普利和扑热息痛 5 种不同药物的应用，评估了该方法的可行性和局限性，其中活性成分的个体剂量范围为 750 mg 至 0.25 mg。确定每种药物的适当样品重量、溶剂和内标，并通过为每种化合物和内标选择最合适的 NMR 信号来进行定量。使用该方法，为了提高分析速度，定量的准确性会有所牺牲，但测量结果提供了出色的精度，并提供了外部校准的可能性。使用光谱相似性计算和微分核磁共振光谱来比较不同的通用品牌并检测最终未声明的成分和污染物。在一个品牌的阿普唑仑片剂中发现了未申报的成分三硬脂酸甘油酯，而在扑热息痛片剂中发现污染物对氨基苯酚的含量超出了立法允许的水平。讨论了该方法的适用性和局限性。 (C) 2021 Elsevier B.V. 保留所有权利。
The illegal trade in counterfeit and fake drugs is a worldwide multi-billion dollar industry, not only generating enormous economic losses, but health problems for the general population, through direct toxicity, treatment failure and the increased generation of antibiotic resistance. Techniques for high-throughput testing of suspect medicines are needed to face the challenges of the problem. In this study we show that with nuclear magnetic resonance spectroscopy (NMR) drug compliance can be verified in a few minutes, providing data on drug identity, purity and quality without the necessity to develop a specific methodology and using a direct extraction with deuterated solvent. The evaluation of the data is facilitated by similarity calculations and differential NMR spectroscopy. The viability and limitations of this method were assessed, with the application on five different drugs, namely sertraline hydrochloride, alprazolam, vitamin D-3, enalapril maleate and paracetamol, in which the individual dosage quantity of the active ingredient ranged from 750 mg down to 0.25 mg. The appropriate sample weight, solvent and internal standard were determined for each drug and quantification was carried out by choosing the most adequate NMR signals for each compound and the internal standard. With the method the accuracy of the quantification is somewhat sacrificed for increased speed in the analysis, but the measurements offer excellent precision and offer the possibility of external calibration. Spectral similarity calculations and differential NMR spectroscopy were used to compare different generic brands and detect eventual undeclared constituents and contaminants. In one brand of alprazolam tablets the undeclared constituent tristearin was found, while in paracetamol tablets the contaminant para-aminophenol was found at a level above the allowed by the legislation. The applicability and limitations of the method are discussed. (C) 2021 Elsevier B.V. All rights reserved.