Combining attenuated total reflectance- infrared spectroscopy and chemometrics for the identification and the dosage estimation of MDMA tablets.

The principal objective of the Belgian Early Warning System on drugs (BEWSD) of the Reitox national focal point is to collect and disseminate information on the appearance of drugs circulating on the local drug market. To this end, one of the actions of BEWSD is to annually collect substances that are circulating on the Belgian summer festivals. Every year a high number of seized samples is collected and submitted to qualitative and quantitative analysis. The goal is twofold: next to the monitoring of the drug market, a surveillance on the quality of drugs is established with main focus on the evolution of MDMA dosages in ecstasy as well as the emergence of new psychoactive substances (NPS). The presented paper focusses on the characterization of ecstasy tablets, seized at summer festivals in the seasons 2016 and 2017. Samples were classically analysed with GC-MS and UV spectroscopy, representing a certain cost and time for analysis. In this paper, an approach is presented based on infrared spectroscopy to first differentiate ecstasy from other party drugs and further quantify MDMA in the tablets. To this end, a comparison was done between NIR and Mid-IR spectroscopy in combination with partial least squares-discriminant analysis (PLS-DA) and -regression (PLS). For the differentiation between MDMA positive and negative tablets, the best results were obtained by NIR and PLS-DA and resulted in a correct classification rate of 96% for an external test set. In addition, for the quantification of MDMA, the best results were also obtained with a PLS model based on NIR spectra. A RMSEP for the external test set of 3.86 was obtained and an R2 value between real and predicted values of 0.88. This means that for the dosage MDMA per tablet, when taking into account the range of masses of the tablets in our sample set, the error varies between 8 mg for low mass tablets and 27.8 mg for high mass tablets. These are acceptable values for a first estimation and give a first indication of the risk the tablet may represent. The presented approach will be of use for on-site analysis. Moreover, when applied in a laboratory environment, it will reduce the workload for the analysis of MDMA tablets and thus liberating resources.

HS-GC-MS method for the analysis of fragrance allergens in complex cosmetic matrices.

Potential allergenic fragrances are part of the Cosmetic Regulation with labelling and concentration restrictions. This means that they have to be declared on the ingredients list, when their concentration exceeds the labelling limit of 10 ppm or 100 ppm for leave-on or rinse-off cosmetics, respectively. Labelling is important regarding consumer safety. In this way, sensitised people towards fragrances might select their products based on the ingredients list to prevent elicitation of an allergic reaction. It is therefore important to quantify potential allergenic ingredients in cosmetic products. An easy to perform liquid extraction was developed, combined with a new headspace GC-MS method. The latter was capable of analysing 24 volatile allergenic fragrances in complex cosmetic formulations, such as hydrophilic (O/W) and lipophilic (W/O) creams, lotions and gels. This method was successfully validated using the total error approach. The trueness deviations for all components were smaller than 8%, and the expectation tolerance limits did not exceed the acceptance limits of ± 20% at the labelling limit. The current methodology was used to analyse 18 cosmetic samples that were already identified as being illegal on the EU market for containing forbidden skin whitening substances. Our results showed that these cosmetic products also contained undeclared fragrances above the limit value for labelling, which imposes an additional health risk for the consumer.

Headspace-gas chromatographic fingerprints to discriminate and classify counterfeit medicines.

Counterfeit medicines are a global threat to public health. These pharmaceuticals are not subjected to quality control and therefore their safety, quality and efficacy cannot be guaranteed. Today, the safety evaluation of counterfeit medicines is mainly based on the identification and quantification of the active substances present. However, the analysis of potential toxic secondary components, like residual solvents, becomes more important. Assessment of residual solvent content and chemometric analysis of fingerprints might be useful in the discrimination between genuine and counterfeit pharmaceuticals. Moreover, the fingerprint approach might also contribute in the evaluation of the health risks different types of counterfeit medicines pose. In this study a number of genuine and counterfeit Viagra(®) and Cialis(®) samples were analyzed for residual solvent content using headspace-GC-MS. The obtained chromatograms were used as fingerprints and analyzed using different chemometric techniques: Principal Component Analysis, Projection Pursuit, Classification and Regression Trees and Soft Independent Modelling of Class Analogy. It was tested whether these techniques can distinguish genuine pharmaceuticals from counterfeit ones and if distinct types of counterfeits could be differentiated based on health risks. This chemometric analysis showed that for both data sets PCA clearly discriminated between genuine and counterfeit drugs, and SIMCA generated the best predictive models. This technique not only resulted in a 100% correct classification rate for the discrimination between genuine and counterfeit medicines, the classification of the counterfeit samples was also superior compared to CART. This study shows that chemometric analysis of headspace-GC impurity fingerprints allows to distinguish between genuine and counterfeit medicines and to differentiate between groups of counterfeit products based on the public health risks they pose.

Evaluation of the residual solvent content of counterfeit tablets and capsules.

A group of counterfeit samples of Viagra and Cialis were screened for their residual solvent content and compared to the content of the genuine products. It was observed that all counterfeit samples had higher residual solvent contents compared to the genuine products. A more diverse range of residual solvents was found as well as higher concentrations. In general these concentrations did not exceed the international imposed maximum limits. Only in a few samples the limits were exceeded. A Projection Pursuit analysis revealed clusters of samples with similar residual solvent content, possibly enabling some future perspectives in forensic research.

A validated GC-MS method for the determination and quantification of residual solvents in counterfeit tablets and capsules.

A fast headspace GC-MS method was developed and validated for the detection and quantification of residual solvents of all three ICH-classes in counterfeit tablets and capsules. The method was validated for 10 solvents, selected based on an initial screening of counterfeit medicinal products. The considered solvents were ethanol, 2-propanol, acetone, ethylacetate, chloroform, carbon tetrachloride, benzene, toluene, dichloromethane and ethylbenzene. The proposed method uses a Phenomenex 624 capillary column (60 m × 0.32 mm; 1.8 µm film thickness) (Phenomenex, Torrance, USA) with an oven temperature program from 60 °C (held for 5 min) to 270 °C at 25 °C/min. 270 °C is held for 10 min. The total run time is 23.4 min. The obtained method was fully validated by applying the "total error" profile. Calibration lines for all components were linear within the studied ranges. The relative bias and the relative standard deviations for all components were smaller than 5%, the ß-expectation tolerance limits did not exceed the acceptance limits of ±10% and the relative expanded uncertainties were acceptable for all of the considered components. A method was obtained for the screening and quantification of residual solvents in counterfeit tablets and capsules, which will allow a fast screening of these products for the presence of residual solvents.