Current Analytical Chemistry - Volume 17, Issue 8, 2021

Recently, different strategies such as personalized therapy, dose adjustment, therapy monitoring and targeted drug delivery (disease-specific localization), were adopted for improving efficacy ratio of medicines that are currently in use. From a therapeutical point of view, to reach the optimal concentrations in the target organ or tissue, it is necessary to increase the administered dose, which is accompanied by an increase in the frequency and intensity of the side effects, many of them undesirable and distressing for the patient. Therefore, designing targeted delivery systems for a specific organ or tissue is the ideal solution, ensuring the necessary concentrations at the site of action and avoiding or at least significantly reducing the side effects. An overview of the modern analytical techniques currently used for the drug delivery systems characterization was intended in this review with a focus on those commonly used.

Background: Numerous sequencing techniques have been progressed since the 1960s with the rapid development of molecular biology studies focusing on DNA and RNA. Methods: A great number of articles, book chapters, websites are reviewed, and the studies covering NGS history, technology and applications to cancer therapy are included in the present article. Results: High throughput next-generation sequencing (NGS) technologies offer many advantages over classical Sanger sequencing with decreasing cost per base and increasing sequencing efficiency. NGS technologies are combined with bioinformatics software to sequence genomes to be used in diagnostics, transcriptomics, epidemiologic and clinical trials in biomedical sciences. NGS technology has also been successfully used in drug discovery for the treatment of different cancers. Conclusion: This review focuses on current and potential applications of NGS in various stages of drug discovery process, from target identification through to personalized medicine.

Raman Spectroscopy is on the verge of becoming a promising tool in Forensic Toxicology with the increasing number of studies in the literature. Raman Spectroscopy, which has been found successful in many areas of forensic sciences and has found its place in routine use, is gaining more importance recently in Forensic Toxicological studies especially with Surface Enhanced Raman Spectroscopy due to its fast, reliable and cost-effective results. In this paper, the forensic toxicological studies carried out by using Raman Spectroscopy are reviewed and discussed with the findings, and suggestions are made regarding the use and study of Raman Spectroscopy in the field of Forensic Toxicology for future applications.

Background: Radiation sterilization is a promising method of obtaining sterile active pharmaceutical ingredients (API), excipients and formulations. One of the best methods of sterilization is to use ionizing radiation. The greatest advantage of ionizing radiation is the fact that it can be conducted at room temperature or lower. Therefore, this procedure of sterilization is reserved for drugs sensitive to the high temperature of autoclaving. Solutions of parenterally administered antibiotics must be absolutely aseptic. Most of the antibiotics are susceptible to degradation at increased temperature and humidity, so radiation is often used to obtain sterile bactericidal drugs. Methods: The available literature and published papers related to radiation sterilization as well as other sterilization methods were collected, analyzed, and reviewed to provide the comprehensive information about the radiation sterilization of antibiotics. The review was critically evaluated and concluded, emphasizing future perspectives for radiation sterilization of antibiotics. Results: The review presented the basic principles, merits, and demerits of radiation sterilization in pharmaceutical samples. Further, the review highlighted the updated summary of the recent advances in terms of the latest regulations and recommendations for radiation sterilization. Conclusion: Radiation sterilization has a promising future in pharmaceutical manufacturing processes. This approach is compatible with various types of material, is easy to control, does not increase the temperature of the process, and from the business point of view - can help to save money and time during manufacturing solid dosage forms of medicines. From the pharmaceutical sense, fully effective sterilization in the terminal step - finished packed product - is the most important advantage of radiation sterilization.

Background: Dopamine agonists are useful drugs for the management of patients with Parkinson's disease in the early and later stages of the disease. Parkinson's disease is a progressive neurodegenerative disease that primarily affects dopamine-producing nerve cells in the brain. They bind to dopamine receptors in nerve cells that regulate body movement and motor function. Electroanalytical methods are used in medicinal, clinical and pharmaceutical research. Voltammetry is one of the most commonly used electroanalytical methods. This review aims to gather and discuss studies of voltammetric methods used in determination of dopamine agonists. Methods: This review includes the use of various voltammetric methods for determination studies of dopamine agonists from pharmaceutical dosage forms and biological samples. These studies were examined in terms of used voltammetric method or methods, working electrode, buffer, pH and validation parameters. Results: Cabergoline, pramipexole, and ropinirole have more studies, while bromocriptine and apomorphine have fewer studies in the literature. Differential pulse voltammetry and square wave voltammetry methods were the most applied methods for the determination of dopamine agonist drugs from pharmaceuticals and biological samples. But, stripping, cyclic and linear sweep voltammetry methods are less applied methods. In these studies, a lot of modified electrodes were developed and used to analyse dopamine agonists. Conclusion: The voltammetric methods provide the determination of therapeutic agents and/or their metabolites in clinical samples at extremely low concentrations without the necessity for the sample pre-treatment or time consuming extraction steps. Also, the modified electrodes and validated voltammetric methods provide good stability, repeatability, reproducibility and high recovery for the analysis of the analyte.

Background: The extraction of vitamins from complex matrices, such as pharmaceutical and biological samples, is a demanding task. Progress in material science is revolutionizing sample preparation, leading to the development of more efficient, sensitive, and selective analytical methods. In particular, the evolution of solid-phase extraction towards miniaturized techniques is closely related to the introduction of nanomaterials as new sorbents. Microextraction techniques, both solid-based and liquid-based, allow for the reduction of solvent and sample volumes, as well as the sample processing times. In many cases, these procedures are also environmentally friendly. Moreover, the substitution of traditional organic solvents with the neoteric ones is another current trend in analytical chemistry. Aims: The aim of this review is to introduce readers to the innovative solutions available for the extraction of vitamins from matrices of different complexity. Methods: Research papers in the literature of the last five years are reviewed, providing a critical description of the most original and interesting sample preparation approaches devoted to vitamin extraction. Results: Among the last five years of literature concerning the analysis of vitamins in the clinical and pharmaceutical sectors, only 40% of works applied some innovative or green approaches to sample preparation. However, a general trend is the reduction of solvent volumes and sample processing times. Conclusion: The great potential of microextraction techniques based on nanomaterials and neoteric solvents has not been fully exploited yet in the clinical and pharmaceutical fields. Considering the high cost of carbon-based nanomaterials, it can be expected that in the near future, liquid microextraction techniques based on neoteric solvents will be more effective for sample preparation. Thanks to their low cost, environmental compatibility, simplicity, speediness and high enrichment factor, these extractive techniques are particularly significant for vitamin analysis.

Background/Aim: Use of nanomaterials in healthcare applications increases in parallel to technological developments. It is frequently utilized in diagnostic procedures, medications and therapeutic implementations. Nanomaterials take place among key components of medical implants, which might be responsible for certain toxic effects on human health at nano-level. In this review, nanotoxicological effects, toxicity determination of nanobiomaterials used in human body and their effects on human health are discussed. Materials and Methods: A detailed review of related literature was performed and evaluated as per nanomaterials and medical implants. Results: The nanotoxic effects of the materials applied to human body and the determination of its toxicity are important. Determination of toxicity for each nanomaterial requires a detailed and multifactorial assessment considering the properties of these materials. Conclusion: There are limited studies in the literature regarding the toxic effects of nanomaterials used in medical implants. Although these implants are potentially biocompatible and biodegradable, it is highly important to discuss nanotoxicological characteristics of medical implants.

Background: The development of innovative approaches in drug analysis is a challenging task for medicine, pharmacy, and engineering sciences. For instance, the requirement of proper dosage forms in releasing active ingredients is crucial. It is essential to analyze drugs in biological liquids for early diagnosis and treatment purposes. Drug analysis is also of great importance to control the quality of pharmaceutical products, test their efficacy, and develop novel drug formulation. The present review is aimed to highlight the most recent spectrophotometric approaches applied to analyze various classes of drugs in biological media and/or dosage forms. Methods: Direct and derivative UV/UV-Vis spectrophotometry and a combination of various techniques with spectrophotometry, such as injection analysis and chemometrics, have most widely been applied in the analysis of dosage forms. In addition, emerging technologies, such as UV imaging allows to obtain the distribution of drug concentration in time-resolved 2D images based on UV light absorption, utilization of nanotechnology, self-assembled nanomaterials, and aptamer-based nanoparticles have gained interests to investigate drug assays and to quantify the proper drug release. Results: Due to their high versatility, ease of application, low cost, and fast response, spectrophotometric methods are one of the most preferable methods providing high accuracy and precision with a wide linear range in drug analysis. Conclusion: Selected examples demonstrating the applicability of spectrophotometric methods in pharmaceutical assays in this review might contribute to the overall importance of the analytical test used in modern pharmaceutical analysis.

Background: Nanotechnology is a promising field of science which deals with the production and utilization of material under nanoscale dimensions. The nanoscale regime provides exceptional applications in various fields of science due to its large surface to volume ratio and many valuable properties. Hence, the production and use of nanomaterials are the prominent areas of modern research. Amongst the nanomaterials, metal oxide NPs have gained much attention due to their vast number of applications in different areas, including electrochemical applications, dye degradation, catalysis, and are known to be the exceptional entities in the battle against different pathogens. The metal oxides are viably synthesized through chemical methods that require the use of many noxious chemicals. Henceforth, it is the demand of the modern world to carry out research on the synthesis of metal oxide nanomaterials through eco-friendly, greener, and non-toxic routes. Thus, various green methods are employed to engineer the metal oxide NPs by using different greener, cheaper, and eco-friendly sources, employing the use of plant extracts, bacteria, fungi and other biological bodies. The present review covered the green synthesis of CuO, ZnO, TiO2 NPs and their applicability towards different pathogens and environmental remediation reported from the year 2015 to date. Objective: The exceptional catalytic properties, environmental, and anti-microbial applications of metal oxide, especially CuO, ZnO, TiO2, are the main highlights of this review articles. The most cost-effective and greener routes for the synthesis of CuO, ZnO, TiO2, are discussed in the present review. To date, various green synthetic methods for the preparation of mentioned nanoparticles and their applicability towards different pathogens and degradation of different hazardous dyes with some electrochemical applications has been thoroughly covered in this review. Conclusion: The biosynthesis of metal oxide NPs using greener and eco-friendly approaches have been the attentive area in the last decade. Green synthesis requires chemical-free active components from biological sources, which act as both the reducing and stabilizing agent for the size and shapecontrolled production of NPs. The future vision of bacterial, fungal, and plant-mediated production of NPs includes the postponement of laboratory-based work to a large industrial scale, exposition of different phytochemicals involved in the biosynthesis of NPs using bioinformatics techniques and stemming the real mechanism involved in preventing the growth of pathogenic bacteria, fungi, and algae. The plant-mediated NPs can have diverse applications in the arena of pharmaceutical, food, and cosmetic industries, and thus, became a vital area of modern research.

Background: Gold nanoparticles (AuNPs) are commonly used in nanomedicine because of their unique spectral properties, chemical and biological stability, and ability to quench the fluorescence of organic dyes attached to their surfaces. However, the utility of spherical AuNPs for activatable fluorescence sensing of molecular processes have been confined to resonance-matched fluorophores in the 500 nm to 600 nm spectral range to maximize dye fluorescence quenching efficiency. Expanding the repertoire of fluorophore systems into the NIR fluorescence regimen with emission >800 nm will facilitate the analysis of multiple biological events with high detection sensitivity. Objective: The primary goal of this study is to determine if spherical AuNP-induced radiative rate suppression of non-resonant near-infrared (NIR) fluorescent probes can serve as a versatile nanoconstruct for highly sensitive detection and imaging of activated caspase-3 in aqueous media and cancer cells. This required the development of activatable NIR fluorescence sensors of caspase-3 designed to overcome the nonspecific degradation and release of the surface coatings in aqueous media. Methods: We harnessed the fluorescence-quenching properties and multivalency of spherical AuNPs to develop AuNP-templated activatable NIR fluorescent probes to detect activated caspase-3, an intracellular reporter of early cell death. Freshly AuNPs were coated with a multifunctional NIR fluorescent dye-labeled peptide (LS422) consisting of an RGD peptide sequence that targets αvβ3-integrin protein (αvβ3) on the surface of cancer cells to mediate the uptake and internalization of the sensors in tumor cells; a DEVD peptide sequence for reporting the induction of cell death through caspase-3 mediated NIR fluorescence enhancement; and a multidentate hexacysteine sequence for enhancing self-assembly and stabilizing the multifunctional construct on AuNPs. The integrin-binding affinity of LS422 and caspase-3 kinetics were determined by competitive radioligand binding and fluorogenic peptide assays, respectively. Detection of intracellular caspase-3, cell viability, and the internalization of LS422 in cancer cells was determined by confocal NIR fluorescence spectroscopy and microscopy. Results: Narrow size AuNPs (13 nm) were prepared and characterized by transmission electron microscopy and dynamic light scattering. When assembled on the AuNPs, the binding constant of LS422 for αvβ3 improved 11- fold from 13.2 nM to 1.2 nM. Whereas the catalytic turnover of caspase-3 by LS422-AuNPs was similar to the reference fluorogenic peptide, the binding affinity for the enzyme increased by a factor of 2. Unlike the αvβ3 positive, but caspase-3 negative breast cancer MCF-7 cells, treatment of the αvβ3 and caspase-3 positive lung cancer A549 cells with Paclitaxel showed significant fluorescence enhancement within 30 minutes, which correlated with caspase-3 specific activation of LS422-AuNPs fluorescence. The incorporation of a 3.5 mW NIR laser source into our spectrofluorometer increased the detection sensitivity by an order of magnitude (limit of detection ~0.1 nM of cypate) and significantly decreased the signal noise relative to a xenon lamp. This gain in sensitivity enabled the detection of substrate hydrolysis at a broad range of inhibitor concentrations without photobleaching the cypate dye. Conclusion: The multifunctional AuNPs demonstrate the use of a non-resonant quenching strategy to design activatable NIR fluorescence molecular probes. The nanoconstruct offers a selective reporting method for detecting activated caspase-3, imaging of cell viability, identifying dying cells, and visualizing the functional status of intracellular enzymes. Performing these tasks with NIR fluorescent probes creates an opportunity to translate the in vitro and cellular analysis of enzymes into in vivo interrogation of their functional status using deep tissue penetrating NIR fluorescence analytical methods.

Background: Determination of a reducing substance based on the reaction between Ce(IV) and a reducing substance and fluorescence detection of Ce(III) generated has been reported as a selective and sensitive method. However, this method could not be applied to the determination of alcohol due to the low reaction rate of alcohol and Ce(IV). Objective: We found that thiosulfate catalytically enhanced the reaction of alcohols (such as, methanol, ethanol, and propanol) and Ce(IV). Utilizing this effect, we developed a new method for the determination of alcohols. Methods: Alcohols were detected using the reaction of Ce(IV) with alcohols in the presence of thiosulfate and fluorescence detection of the Ce(III) generated by the reaction. Results: In the presence of thiosulfate, an increase in fluorescence intensity was detected by injecting alcohol at concentrations of several millimolar, whereas it was not observed even at the concentration of 10% v/v (2 M for ethanol) in the absence of thiosulfate. The optimum detection conditions were determined to be 4.0 mM Ce(IV) sulfate and 0.50 mM thiosulfate, and the detection limit (S/N = 3) of ethanol under these conditions was 1 mM. In the calibration curves, changes in the slope were observed when the alcohol concentrations were approximately 10–25 mM. Using a thiosulfate solution containing ethanol as the reaction solution, a calibration curve without any change in slope was obtained, although the concentration of ethanol at the detection limit increased. The alcohols in the liquor and fuel were successfully analyzed using the proposed detection method as a postcolumn reaction. Conclusion: This new alcohol detection method using a versatile fluorescence detector can be applied to the postcolumn reaction of HPLC omitting need of time-consuming pretreatment processes.

Background: Folic acid (pteroylglutamic acid, FA), known as a water-soluble vitamin of B complex family, plays an important role in the human body. However, excess intake of FA would mask the vitamin B12 deficiency symptoms, which may lead to other health risks. Therefore, it is very important to develop a method for the sensitive and selective determination of FA in natural sources, fortified foods and multivitamin preparations. Methods: An electrochemical sensor was fabricated for the analysis of FA, which was based on electropolymerized molecularly imprinted poly (o-aminophenol) film and reduced graphene oxide decorated with Au nanoparticles composites (rGO-AuNPs). The transmission electron microscope, cyclic voltammetry, electrochemical impedance spectroscopy and differential pulse voltammetry were utilized for the characterization of the imprinted polymer film. Results: Under the optimized experimental conditions, the proposed sensor exhibited two distinct linear responses ranging from 0.02 to 0.8 μmol L^-1 and 0.8 to 10 μmol L^-1 towards the concentrations of FA, and the detection limit was found to be 2.8 nmol L^-1 (S/N=3). The molecularly imprinted film proposed was also found to exhibit comparatively high selectivity toward folic acid against structurally similar analogues, and the preparation of the sensor was simple and reproducible. Conclusion: In this work, a molecularly imprinted film fabricated on an rGO-AuNPs modified electrode was developed for the sensitive and selective determination of FA. Furthermore, the method was applied to the detection of FA in infant formula milk, multivitamin tablets and blood serum sample with satisfactory results.