Dos Santos Ribeiro Helen Sant'Ana, Dagnino Denise, Schripsema Jan
Grupo Metabolômica, Laboratório de Ciências Químicas, Universidade Estadual do Norte Fluminense, Av. Alberto Lamego, 2000, Campos dos Goytacazes, 28013-602, Brazil.
Grupo Metabolômica, Laboratório de Biotecnologia, Universidade Estadual do Norte Fluminense, Av. Alberto Lamego, 2000, Campos dos Goytacazes, 28013-602, Brazil.
J Pharm Biomed Anal. 2021 May 30;199:114040. doi: 10.1016/j.jpba.2021.114040. Epub 2021 Mar 26.
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, 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.
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，还因直接毒性、治疗失败以及抗生素耐药性增加给普通民众带来健康问题。面对这一问题的挑战，需要高通量检测可疑药品的技术。在本研究中，我们表明利用核磁共振波谱法（NMR）可在几分钟内验证药品合规性，无需开发特定方法，通过氘代溶剂直接萃取即可提供有关药品身份、纯度和质量的数据。相似性计算和差分核磁共振波谱法有助于数据评估。评估了该方法的可行性和局限性，并将其应用于五种不同的药物，即盐酸舍曲林、阿普唑仑、维生素D、马来酸依那普利和对乙酰氨基酚，其中活性成分的单剂量范围从750毫克到0.25毫克。确定了每种药物的合适样品重量、溶剂和内标，并通过为每种化合物和内标选择最合适的NMR信号进行定量。该方法在分析速度提高的同时，定量准确性有所牺牲，但测量具有出色的精密度，并提供了外部校准的可能性。利用光谱相似性计算和差分核磁共振波谱法比较不同品牌的仿制药，并检测可能未申报的成分和污染物。在一个品牌的阿普唑仑片中发现了未申报成分硬脂酸甘油三酯，而在对乙酰氨基酚片中发现污染物对氨基苯酚的含量高于法定允许水平。讨论了该方法的适用性和局限性。
