French National Agency for Medicines and Health Products Safety, Laboratory Controls Division, 635 rue de la Garenne, 34740 Vendargues, France.
Hospital Center of Narbonne, Boulevard Docteur Lacroix, 11108 Narbonne, France.
J Pharm Biomed Anal. 2018 Jan 30;148:316-323. doi: 10.1016/j.jpba.2017.10.005. Epub 2017 Oct 19.
Falsified drugs are a threat to the health of patients. The analytical control of such products contributes to the fight against this global issue. Raman chemical imaging is a method that relies on consecutive measurements at the surface of a sample, combining spectroscopy, microscopy and chemometrics. This article explores the capabilities of this analytical technique proposing an innovative methodology with spectroscopic screening for the identification of chemical compounds and the direct quantification of the active substance (without prior calibration). Two chemometric methods were used: Multivariate Curve Analysis - Alternate Least Squares for the qualitative analysis and Direct Classical Least Squares for the quantitative analysis. The methodology was optimized with samples prepared in the laboratory and validation parameters were studied. The methodology was then applied to real (authentic and falsified) samples of Viagra and Plavix. Despite the presence of fluorescence emission in some samples, the methodology succeeded in the detection of active pharmaceutical ingredients, and in the discrimination of three salts of clopidogrel (in generic formulations of Plavix). The quantitative deviation from the reference method ranged from -15% to +24% of the active substance content. This deviation may be considered to be acceptable since it is sufficient for assessing the risk to the health of patients and for quickly alerting the health authorities.
假药是对患者健康的威胁。对这类产品进行分析性控制有助于应对这一全球性问题。拉曼化学成像（Raman chemical imaging）是一种依赖于对样品表面进行连续测量的方法，结合了光谱学、显微镜和化学计量学。本文探讨了这种分析技术的能力，提出了一种具有创新性的方法，即通过光谱筛选进行化合物的识别和活性物质的直接定量（无需预先校准）。使用了两种化学计量学方法：多元曲线分析-交替最小二乘法用于定性分析，直接经典最小二乘法用于定量分析。该方法使用实验室制备的样品进行了优化，并研究了验证参数。然后将该方法应用于真实（真实和伪造）的伟哥和氯吡格雷（Plavix）样本。尽管一些样品存在荧光发射，但该方法成功地检测到了活性药物成分，并对氯吡格雷的三种盐（Plavix 的仿制药）进行了区分。与参考方法相比，活性物质含量的定量偏差在-15%至+24%之间。这种偏差可以认为是可以接受的，因为它足以评估对患者健康的风险，并迅速向卫生当局发出警报。
