Authenticating medicines with dual laser handheld Raman spectroscopy

The World Health Organisation (WHO) defines counterfeit medicines as those that have been "deliberately and fraudulently mislabelled according to identity or source'"1. Such illegitimate drugs can have defects in their active pharmaceutical ingredients (APIs), excipients or coating, or their packaging might have been tampered with. The harm resulting from them is unpredictable and can range from treatment ineffectiveness to drug resistance and even death. Additionally, drug counterfeiting is not limited to a class or formulation type and can be encountered anywhere in the wholesale supply chain. In this respect, rapid and mobile techniques that can authenticate medicines where they are encountered are favourable

Evaluating handheld spectroscopic techniques for identifying counterfeit branded and generic medicines worldwide

Counterfeit medicines represent a global public health problem which accounts for 10% of the world market including 50% in some countries. Medicine counterfeiting can occur to any class of medicines, any type of formulation and can be encountered anywhere in the world. Consequently, rapid methods are needed to identify counterfeit medicines at their site of origin. Handheld spectroscopic techniques offer this advantage. This work features the use of nearinfrared (NIR) and Raman spectroscopic methods for identification of counterfeit medicines obtained worldwide. A total of 300 branded and generic medicines were measured using five spectroscopic instruments; being two NIR and three Raman (of different laser wavelength). Spectra obtained from these instruments were exported into a multiparadigm numerical computing environment where multivariate classification and regression algorithms were applied. The results showed that the selection of the technique depended on the type of medicine used. Thus, NIR was more successful in authenticating branded medicines where the physicochemical properties were of interest. On the other hand, Raman was ideal for authenticating generic medicines where the chemical signature of the API and/or excipient(s) were the subject of analyses. Furthermore, where adequate number of batches were available, the application of multivariate algorithms offered more accurate classification of the medicines. In summary, both techniques alongside multivariate algorithms proposed rapid methods for identifying counterfeit branded and generic medicines worldwide

From "Special K" to "Special M" : The Evolution of the Recreational use of Ketamine and Methoxetamine

Objective: To review the recreational use of ketamine (‘Special K’; KET) and explore the recent diffusion of its new derivative methoxetamine (‘Special M’; MXE). Methods: The literature search on the non-clinical/recreational use of KET and MXE was carried out in a range of medical databases. Considering the limitations of peer-reviewed information, data were integrated with a qualitative assessment of a range of websites, drug fora and other online resources including. Results: The recreational use of KET has started since its discovery in 1962. This was due to its rapid onset, short duration of action, and peculiar psychotropic effects (‘K-hole’). The latter effect ranges from confusion to dissociation and depersonalization (near-death experience). However, KET abuse is often associated with physical and psychological side effects of which the worst is urological/bladder toxicity. Recently, MXE has emerged as a legal and ‘bladder friendly’ KET alternative. MXE presents with the same dissociative effect of KET but with slower onset and longer duration of action. However, MXE seems to be associated with worse side effects than KET, ranging from mood disturbances/suicidal attempts to acute cerebellar toxicity. Conclusions: After 50 years of its discovery, KET has led to the emergence of MXE. However, this latter derivative does not appear to be a safer alternative to KET itself.Peer reviewe

Design of a Statistics Lecture for Multidisciplinary Postgraduate Students Using a Range of Tools and Techniques

Teaching statistics is a critical and challenging issue especially to students from multidisciplinary and diverse postgraduate backgrounds. Postgraduate research students require statistics not only for the design of experiments; but also for data analysis. Students often perceive statistics as a complex and technical subject; thus, they leave data analysis to the last moment. The lecture needs to be simple and inclusive at the same time to make it comprehendible and address the learning needs of each student. Therefore, the aim of this work was to design a simple and comprehendible statistics lecture to postgraduate research students regarding ‘Research plan, design and data collection’. The lecture adopted the constructive alignment learning theory which facilitated the learning environments for the students. The learning environment utilized a student-centered approach and used interactive learning environment with in-class discussion, handouts and electronic voting system handsets. For evaluation of the lecture, formative assessment was made with in-class discussions and poll questions which were introduced during and after the lecture. The whole approach showed to be effective in creating a learning environment to the students who were able to apply the concepts addressed to their individual research projects

The effects and toxicity of cathinones from the users' perspectives: A qualitative study.

OBJECTIVE: The objective of this study is to explore the users' perspectives regarding the effects and toxicity of cathinones. METHODS: A systematic search of Internet discussion forums yielded 303 threads relevant to the research objectives. The threads were analysed by conventional content analysis where concepts were developed from codes and themes. RESULTS: The study identified 3 main themes in relation to cathinone use, effects, and toxicity. The first theme considered the modalities of intake of cathinones in relation to the derivative taken (mainly mephedrone, 3-methylmethcathinone, and methylenedioxypyrovalerone), route of administration (eyeballing, insufflation, smoking, intravenous, oral, rectal, and sublingual), multidrug use, and purity of the cathinone derivative. The second theme characterised the main effects of cathinones, that is, increased energy, euphoria, and empathogenic. Toxic effects were reported regarding the nervous system (anxiety, hallucinations, nervousness, and paranoia), cardiovascular system (angina, myocardial infarction, and tachycardia), skin (discolouration, itching, and allergy), and renal system (difficulty in urination). Drug-drug interactions were also reported including multiple drug use between cathinones, stimulants, depressants, and hallucinogens. CONCLUSIONS: The Internet discussion forums provide useful sources of information regarding the effects and toxicity of cathinones, which can be taken into account when assessing the safety of drugs

Rapid Detection of Synthetic Cannabinoid Receptor Agonists Impregnated into Paper by Raman Spectroscopy

The last decade has witnessed the emergence of new psychoactive substances that are analogues of classical drugs of abuse in order to escape the regulations surrounding the latter drugs. These drugs were of both herbal and synthetic origin and were advertised initially as ‘legal highs’; thus, they were perceived as safe by users. Hence, upon their emergence, they were not controlled by the Misuse of Drugs Act 1971, which contributed to their popularity and increased sales online and within street markets. In 2016, the Psychoactive Substance Act introduced a blanket ban on all new psychoactive substances except for caffeine, alcohol, and nicotine. This in turn, contributed to the change in the sale of new psychoactive substances products that have been sold as concealed in different matrices, including herbal products, papers, fabrics, and textiles. Concealing drugs in paper has been very popular, especially since the drug product is of lightweight and can be sent via postal services. However, new psychoactive concealed in papers are toxic not only to the users; but also, to the person handling them (i.e. mail employees). One of the classes of new psychoactive substances that have been commonly concealed in papers and that have been linked to toxicity and hospitalization cases is synthetic cannabinoids. Therefore, there is a need to identify new psychoactive substances concealed in papers non-destructively and rapidly to prevent toxicity linked to them. Handheld Raman spectroscopy offers this advantage as it is of lightweight and carries the sample to the matrix. Therefore, this work used handheld Raman spectroscopy for identifying synthetic cannabinoids concealed in papers using Raman spectroscopy combined with machine learning analytics. Synthetic cannabinoid and paper samples were measured non-destructively using a handheld Raman spectrometer equipped with a 1064 nm laser wavelength. Spectral data was exported into Matlab 2020b where machine learning analytics including identification and prediction was. The results showed that Raman spectroscopy could identify specific synthetic cannabinoids in papers that were either deposited on the surface of the paper or diffused inside the paper substrate. When machine learning analytics were applied to the Raman spectra of the papers, quantitative information was obtained regarding the amount of synthetic cannabinoid deposited on the paper surface. In summary, handheld Raman spectroscopy could identify and quantify synthetic cannabinoids on paper rapidly and non-destructively. Future work involves testing other classes of new psychoactive substance and applying deep learning analytic

Evaluation of portable near-infrared spectroscopy for authentication of mRNA based COVID-19 vaccines

Since its identification in 2019, Covid-19 has spread to become a global pandemic. Until now, vaccination in its different forms proves to be the most effective measure to control the outbreak and lower the burden of the disease on healthcare systems. This arena has become a prime target to criminal networks that spread counterfeit Covid-19 vaccines across the supply chain mainly for profit. Counterfeit vaccines provide false sense of security to individuals, heightens the risk of exposure and outbreak of the virus, and increase the risk of harm linked to Covid-19 infection. Moreover, the increase in counterfeit vaccines feeds hesitancy towards vaccination and erodes the trust in mass immunisation programmes. It is therefore of paramount importance to work on rapid and reliable methods for vaccine authentication. Subsequently this work utilised a portable and non-destructive near infrared (NIR) spectroscopic method for authentication of Covid-19 vaccines. A total of 405 Covid-19 vaccines samples, alongside their main constituents, were measured as received through glass vials. Spectral quality and bands were inspected by considering the raw spectra of the vaccines. Authentication was explored by applying principal component analysis (PCA) to the multiplicative scatter correction-first derivative spectra. The results showed that NIR spectra of the vaccine featured mainly bands corresponding to the mRNA active ingredient. Fewer bands corresponded to the excipients and protein spectra. The vaccines NIR spectra were strongly absorbing with maximum absorbances up to 2.7 absorbance units and that differentiated them from samples containing normal saline only (constituent reported for counterfeit Covid-19 vaccines). Clustering based on PCA offered optimal authentication of Covid-19 vaccines when applied over the range of 9000-4000 cm-1These findings shed light on the potential of using NIR for analysing Covid-19 vaccines and presents a rapid and effective initial technique for Covid-19 vaccine authentication

Evaluation of portable near-infrared spectroscopy for authentication of mRNA based COVID-19 vaccines

Since its identification in 2019, Covid-19 has spread to become a global pandemic. Until now, vaccination in its different forms proves to be the most effective measure to control the outbreak and lower the burden of the disease on healthcare systems. This arena has become a prime target to criminal networks that spread counterfeit Covid-19 vaccines across the supply chain mainly for profit. Counterfeit vaccines provide false sense of security to individuals, heightens the risk of exposure and outbreak of the virus, and increase the risk of harm linked to Covid-19 infection. Moreover, the increase in counterfeit vaccines feeds hesitancy towards vaccination and erodes the trust in mass immunisation programmes. It is therefore of paramount importance to work on rapid and reliable methods for vaccine authentication. Subsequently this work utilised a portable and non-destructive near infrared (NIR) spectroscopic method for authentication of Covid-19 vaccines. A total of 405 Covid-19 vaccines samples, alongside their main constituents, were measured as received through glass vials. Spectral quality and bands were inspected by considering the raw spectra of the vaccines. Authentication was explored by applying principal component analysis (PCA) to the multiplicative scatter correction-first derivative spectra. The results showed that NIR spectra of the vaccine featured mainly bands corresponding to the mRNA active ingredient. Fewer bands corresponded to the excipients and protein spectra. The vaccines NIR spectra were strongly absorbing with maximum absorbances up to 2.7 absorbance units and that differentiated them from samples containing normal saline only (constituent reported for counterfeit Covid-19 vaccines). Clustering based on PCA offered optimal authentication of Covid-19 vaccines when applied over the range of 9000–4000 cm-1These findings shed light on the potential of using NIR for analysing Covid-19 vaccines and presents a rapid and effective initial technique for Covid-19 vaccine authentication

Forensic Toxicology Laboratory Guidelines: Analytical Method Validation (Version 2.0)

Since postmortem forensic toxicology involves analyzing body fluids and organs from death cases, interpreting that information and studying the sudden unexpected and/or unexplained deaths as coroner’s cases or fall under the jurisdiction of the medical examiner. Reliable results and valid analytical data are an essential requirement for proper interpretation of forensic toxicology cases, especially when evaluating scientific studies and daily routine work, and when presenting any toxicological findings as criminal evidence. In contrast, the results of unreliable analyses can be disputed in court and can also lead to unfair legal judgments against the defendant, or can result in wrong treatment in cases of rehabilitation of patients. In order to establish strong evidence and make a correct decision, the lab is asked to give high quality data that are based on reliable analytical methods. For that reason, all new analytical methods used in forensic toxicology including the clinical diagnosis of causes of death require careful care during the development of the analytical method and during its application. This is also an urgent need in the context of quality management and accreditation, especially as those issues have become increasingly important in the science of poisons and drug analysis in recent years