Clustering of Tadalafil API Samples According to their Manufacturer in the Context of API Falsification Detection.

This paper reports the results of the active pharmaceutical ingredient (API) fingerprint study, organised by the General European Official Medicines Control Laboratory Network (GEON), on tadalafil. A classical market surveillance study, evaluating compliance to the European Pharmacopoeia, was combined with a fingerprint study, the latter to obtain characteristic data for the different manufacturers, allowing the network laboratories to conduct authenticity tests for future samples, as well as to detect substandard and falsified samples. In total, 46 tadalafil API samples from 13 different manufacturers were collected. For all samples fingerprint data was collected through analysis of impurities and residual solvents, mass spectrometric screening, X-ray powder diffraction and proton nuclear magnetic resonance (1H-NMR). Chemometric analysis revealed that all manufacturers could be characterised based on the impurity, residual solvent and 1H-NMR data. Future suspicious samples in the network will therefore be analysed with these techniques in order to attribute the sample to one of the manufacturers. If the sample cannot be attributed, a more profound investigation will be necessary to reveal the origin of the sample. In cases where the suspect sample is claimed to be from one of the manufacturers included in this study, analysis can be limited to the test distinguishing that manufacturer.

GEONs API fingerprint project: Selection of analytical techniques for clustering of sildenafil citrate API samples.

Through its Active Pharmaceutical Ingredient Working Group (API-WG) the General European Official Medicines Control Laboratory (OMCL) Network (GEON), co-ordinated by the European Directorate for the Quality of Medicines & HealthCare (EDQM), regularly organises market surveillance studies for specific APIs for conformity to their monograph in the European Pharmacopoeia. During the past years some studies were combined with a fingerprint study of the APIs. The idea is to obtain a fingerprint for each manufacturer of the API under investigation, allowing the OMCL network to identify future samples as well as to detect substandard and falsified APIs. This paper reports the results of the latest fingerprint study, organised on sildenafil citrate API samples. Seventy-nine samples from 14 different manufacturers were collected throughout the Network. Fingerprint data was collected through Mid-Infrared spectroscopy, Raman spectroscopy, liquid chromatography for related substances, gas chromatography for residual solvents, X-ray diffraction and Nuclear Magnetic Resonance (NMR) spectroscopy. Chemometrics applied to the collected data showed that all manufacturers could be discriminated based on the data of only three of these tests, i.e. gas chromatography for residual solvents, X-ray diffraction and proton NMR. Suspicious API samples for sildenafil citrate will therefore be analysed in the future with the selected techniques in order to link the sample to a manufacturer or demonstrate the absence of such link. If the sample cannot be attributed to one of the manufacturers, further analysis and research on provenance and identity will be required. Of course, if the suspected sample claims to originate from one of the manufacturers included in the study, analysis can be limited to the test distinguishing this manufacturer.

Selectivity of identification of compounds from the group of phosphodiesterase-5 inhibitors (PDE-5i) in falsified products from the Polish market using attenuated total reflectance Fourier transform infrared spectroscopy and X-ray powder diffraction.

Falsified drugs are a growing problem and a great threat all over the world. Searching for easy, fast, not expensive and reproducible methods for identification of active pharmaceutical ingredients (APIs) is an important issue. The application of ATR-IR technique for identification of phosphodiesterase-5 inhibitors (PDE-5i) in falsified products from the Polish market has been demonstrated. Furthermore, the strategy of confirmation of the product's originality inaquick and easy way has been developed. The advantages of this application are: exceptional simplicity, very short measurement time, high selectivity inrelation to structurally similar substances and almost no sample preparation. After validation, developed strategy has been successfully introduced into routine analysis.

Strategy for identification of new psychoactive substances in illicit samples using attenuated total reflectance infrared spectroscopy.

New strategy has been developed for the identification of novel psychoactive substances (NPS) in illicit samples. The methodology was based on the use of attenuated total reflectance Fourier transform infrared spectroscopy (ATR-IR). First pass screening by ATR-IR allows known substances to be rapidly identified, while any non-matching samples are qualified by complementary analytical techniques and then feed back into the spectral libraries. Compounds' identification by ATR-IR was based on the correlation coefficient value. After validation, developed strategy was successfully introduced into routine analysis. Thirty one NPS have been identified in forty five samples. One new opioid was identified and new ATR-IR spectra were acquired, not reported in commercial libraries yet. ATR-IR enabled distinguishing between closely related compounds, even structural isomers. It proved to be an easy and very reproducible tool for screening analysis of NPS, in less than one minute, with no sample destruction, even for very little amount of a sample. Developed and validated strategy may be introduced by other laboratories.