Mass spectrometry (MS), a core technology for proteomics and metabolomics, is currently being developed for clinical applications. The identification of microorganisms in clinical samples using matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry (MALDI-TOF MS) is a representative MS-based proteomics application that is relevant to daily clinical practice. This technology has the advantages of convenience, speed, and accuracy when compared with conventional biochemical methods. MALDI-TOF MS can shorten the time used for microbial identification by about 1 day in routine workflows. Sample preparation from microbial colonies has been improved, increasing the accuracy and speed of identification. MALDI-TOF MS is also used for testing blood, cerebrospinal fluid, and urine, because it can directly identify the microorganisms in these liquid samples without prior culture or subculture. Thus, MALDI-TOF MS has the potential to improve patient prognosis and decrease the length of hospitalization and is therefore currently considered an essential tool in clinical microbiology. Furthermore, MALDI-TOF MS is currently being combined with other technologies, such as flow cytometry, to expand the scope of clinical applications.

Current Status of Matrix-Assisted Laser Desorption/Ionization-Time-of-Flight Mass Spectrometry (MALDI-TOF MS) in Clinical Diagnostic Microbiology.

In recent years, bioanalytical surface-enhanced Raman spectroscopy (SERS) has blossomed into a fast-growing research area. Owing to its high sensitivity and outstanding multiplexing ability, SERS is an effective analytical technique that has excellent potential in bioanalysis and diagnosis, as demonstrated by its increasing applications in vivo. SERS allows the rapid detection of molecular species based on direct and indirect strategies. Because it benefits from the tunable surface properties of nanostructures, it finds a broad range of applications with clinical relevance, such as biological sensing, drug delivery and live cell imaging assays. Of particular interest are early-stage-cancer detection and the fast detection of pathogens. Here, we present a comprehensive survey of SERS-based assays, from basic considerations to bioanalytical applications. Our main focus is on SERS-based pathogen detection methods as point-of-care solutions for early bacterial infection detection and chronic disease diagnosis. Additionally, various promising in vivo applications of SERS are surveyed. Furthermore, we provide a brief outlook of recent endeavours and we discuss future prospects and limitations for SERS, as a reliable approach for rapid and sensitive bioanalysis and diagnosis.

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Surface-enhanced Raman spectroscopy for bioanalysis and diagnosis

The discovery of a “new” psychoactive substance is a relatively exceptional event, while the regulatory response usually involved the assessment of risks to public health and inclusion of the novel substance in the national list of controlled substances. However, in recent years we have witnessed the rapid emergence of new chemical substances, which elude international control and pose a challenge to existing processes and a threat to the credibility of control systems. We currently review and present characteristics of these legal and illegal new substances and issues regarding their global monitoring and regulatory measures already taken, or in the process of being taken, for their control. The concept of prohibition applied in active substance-related legislation is rather hazard ridden as balance is required between the ban on substances of potential therapeutic use and the access on the market of high-risk substances. Current and future laws regarding psychoactive compounds.

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Worldwide legislative challenges related to psychoactive drugs.

Four deaths that seemed to have been caused by a designer drug occurred within a 3-week period in Sendai, Japan. In each case, the decedent possessed the same sachet, labeled "Heart Shot BLACK", which contained a dried plant material with an aromatic scent. It was revealed in our analysis that the product contained a synthetic cannabinoid receptor agonist, 5-fluoro ADB (methyl 2-[1-(5-fluoropentyl)-1H-indazole-3-carboxamide]-3,3-dimethylbutanoate, also known as 5-fluoro MDMB-PINACA), which is now classified as a restricted designer drug in Japan after it caused several casualties. For standard samples, the detection of 5-fluoro ADB in whole blood in the calibration range (0.04-4 ng/mL) was successful with recoveries of 94.6-98.1%, limits of detection of 6 pg/mL, and limits of quantification of 40 pg/mL. The intraday and interday precisions were 0.9-4.8% and 1.1-6.6%, respectively. The bias was -1.1 to 2.9%. We were able to confirm that 5-fluoro ADB was present in the blood of all four decedents at a concentration of 0.11-1.92 ng/mL. From the autopsy, toxicological findings, and circumstances surrounding the cases, it was considered that inhalation of 5-fluoro ADB could have contributed to the deaths. However, the extent to which 5-fluoro ADB contributed to the deaths remains unclear due to the current lack of toxicological information on the compound. In future research, the toxicity of 5-fluoro ADB in humans and the mechanism underlying this effect need to be elucidated.

Identification of 5-Fluoro ADB in Human Whole Blood in Four Death Cases.

Purpose of review Abuse of new psychoactive substances (NPS) has been a new global concern. So far, there has been no international consensus on legislative control of NPS. Scrutiny of Taiwan's illegal drug use history reveals that legislation and policy play an important role in tackling the drug issues. Recent findings Since the early 2000s, use of club drugs (mostly NPS) has become popular in local rave parties and dance clubs in Taiwan. Some NPS, such as ketamine, synthetic cathinones, and para-methoxymethamphetamine, have posed a risk to public health and a challenge to drug policy. Summary The illegal drug use history in Taiwan was firstly briefly reviewed, and the recent NPS use situation was depicted. Heroin and methamphetamine have been the most predominant drugs, but NPS such as ketamine and synthetic cathinones have become a new issue. The toxicological profiles of commonly abused NPS in Taiwan, although limited, were discussed. By comparison of the legislative mechanism for NPS control between Taiwan, South Korea, and Japan, it was found that timely and flexible legislative mechanism(s) is essential for early identification, surveillance, and comprehensive evaluation. In addition, researches on NPS epidemiology and toxicology are needed to firm up evidence-based strategies for effective prevention, treatment, and harm reduction measures.

New psychoactive substances in Taiwan: challenges and strategies.

Prevalence of new psychoactive substances in Northeast Asia from 2007 to 2015.

To intoxicated patients in the emergency room, toxicological analysis can be considerably helpful for identifying the involved toxicants. In order to develop a urine multi-drug screening (UmDS) method, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) were used to determine targeted and unknown toxicants in urine. A GC-MS method in scan mode was validated for selectivity, limit of detection (LOD) and recovery. An LC-MS-MS multiple reaction monitoring (MRM) method was validated for lower LOD, recovery and matrix effect. The results of the screening analysis were compared with patient medical records to check the reliability of the screen. Urine samples collected from an emergency room were extracted through a combination of salting-out assisted liquid-liquid extraction (SALLE) and hybrid protein precipitation/solid phase extraction (hybrid PPT/SPE) plates and examined by GC-MS and LC-MS-MS. GC-MS analysis was performed as unknown drug screen and LC-MS-MS analysis was conducted as targeted drug screen. After analysis by GC-MS, a library search was conducted using an in-house library established with the automated mass spectral deconvolution and identification system (AMDISTM). LC-MS-MS used Cliquid®2.0 software for data processing and acquisition in MRM mode. An UmDS method by GC-MS and LC-MS-MS was developed by using a SALLE-hybrid PPT/SPE and in-house library. The results of UmDS by GC-MS and LC-MS-MS showed that toxicants could be identified from 185 emergency room patient samples containing unknown toxicants. Zolpidem, acetaminophen and citalopram were the most frequently encountered drugs in emergency room patients. The UmDS analysis developed in this study can be used effectively to detect toxic substances in a short time. Hence, it could be utilized in clinical and forensic toxicology practices.

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Junhui Lee

Papers

Prevalence of new psychoactive substances in Northeast Asia from 2007 to 2015.

Urine Multi-drug Screening with GC-MS or LC-MS-MS Using SALLE-hybrid PPT/SPE.