RESUMEN
The authentication of the packaging represents an important step in the investigation of suspected counterfeits of pharmaceutical products. The visual comparison with a retained sample is the first step to detect a counterfeited packaging. Due to the improvement of technologies like printing, the emergence of counterfeits with a better appearance can be observed. Moreover counterfeits are nowadays often a combination of fake and genuine parts that have been manipulated. Authenticating each part of the product is important in the frame of the investigation to understand how the counterfeiters proceed, and which prevention measures should be taken. Lab instruments like spectrometers can help confirm counterfeits of packaging for packaging components on which visually, no difference with a reference would be observed. In this study several analytical tools were evaluated to help support the authentication of the primary and secondary packaging of one medicinal product as an example using seven reference materials and five counterfeits. In some cases, visual examination of the packaging already enabled to detect counterfeits of the studied features. Also the boxes, leaflets and vials have been analysed with Infrared (IR) spectroscopy, Raman microspectroscopy, X-ray fluorescence (XRF) spectroscopy, Scanning Electron Microscopy (SEM) and microcomputed tomography (microCT). According to the obtained results, IR and XRF could support the visual examination of the different packaging components. Despite the small amount of counterfeits, relevant links could also be detected between the studied cases based on the packaging characteristics.
Asunto(s)
Medicamentos Falsificados , Embalaje de Medicamentos , Diseño de Equipo , Humanos , Tinta , Microscopía Electrónica de Rastreo , Papel , Análisis Espectral , Microtomografía por Rayos XRESUMEN
A number of drugs can cause precipitates within renal tubules leading to crystal nephropathy. Crystal nephropathy is usually an exposure-related finding and is not uncommon in preclinical studies, where high doses are tested. An understanding of the nature of precipitates is important for human risk assessment and further development. Our aim was to investigate the ability of various imaging techniques to detect the presence of drugs or metabolites in renal crystals. We applied matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS) imaging, Raman and infrared microspectroscopy, scanning electron microscopy coupled with energy dispersive X-ray (SEM/EDX) spectroscopy and standard histopathology to cases of drug-induced crystal nephropathy, induced in rodents and primates by 4 compounds. MALDI-FTICR MS imaging enabled the identification of the drug-related crystal content in all 4 cases of nephropathy, without reference material and with high accuracy. Crystals were composed of unchanged parent drug and/or metabolites. Similar results were obtained using Raman and infrared microspectroscopy for 2 compounds. In the absence of reference standards of metabolites, Raman and infrared microspectroscopy showed that the crystals consisted of components similar, but not identical, to the administered drug for the other compounds, a limitation for these techniques. SEM/EDX showed which counter ions were colocalized with the identified drug-related material, complementing the MALDI-FTICR MS findings. Therefore, we recommend MALDI-FTICR MS as a first-line methodology to characterize crystal nephropathies. Raman and infrared microspectroscopy may be useful when MALDI-FTICR MS imaging cannot be applied. SEM/EDX could be considered as a complementary technology.
Asunto(s)
Lesión Renal Aguda/diagnóstico por imagen , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico por imagen , Riñón/efectos de los fármacos , Preparaciones Farmacéuticas/química , Animales , Cristalización , Evaluación Preclínica de Medicamentos , Riñón/diagnóstico por imagen , Macaca fascicularis , Ratones , Estructura Molecular , Preparaciones Farmacéuticas/análisis , Ratas , Especificidad de la Especie , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Espectrofotometría Infrarroja , Espectrometría RamanRESUMEN
Vibrational and X-ray spectroscopic techniques are based on the interaction between radiation and matter. This interaction produces various signals that can be detected and that contain information about the morphology, structure or composition of molecules analyzed. When combined together, these complementary techniques are very powerful and facilitate the identification of the samples investigated. Nevertheless, prior sample preparation plays an important role in this identification, since it should allow combining analytical methods without damaging the samples. Through 5 case studies involving visible particles found in various containers, this article shows how an accurate sample preparation procedure associated to a combination of Infrared, Raman and energy dispersive X-ray (EDX) spectroscopies applies for the troubleshooting of foreign matters in pharmaceutical drug products. The forensic investigation procedure proved to be successful for the precise identification of samples.
Asunto(s)
Soluciones Farmacéuticas/química , Industria Farmacéutica/métodos , Espectrofotometría Infrarroja/métodos , Espectrometría Raman/métodos , Vibración , Rayos XRESUMEN
Biomedical device and medicine product manufacturing are long processes facing global competition. As technology evolves with time, the level of quality, safety and reliability increases simultaneously. Micro Computer Tomography (Micro CT) is a tool allowing a deep investigation of products: it can contribute to quality improvement. This article presents the numerous applications of Micro CT for medical device and pharmaceutical packaging analysis. The samples investigated confirmed CT suitability for verification of integrity, measurements and defect detections in a non-destructive manner.