Current Medicinal Chemistry - Volume 25, Issue 33, 2018

A large variety of analytical techniques are available to meet the needs of characterization of solid samples. But, when solid drug delivery systems are concerned we are faced with demanding methodologies which have to compile capabilities of analytical techniques in regard to large diversity of structures and surface functionality of analyzed adsorbent carriers. In this review, the most commonly used analytical techniques are presented with their basic principles, advantages and disadvantages in applications of interest. Adsorbent carriers are widely used today as ingredients in the formulation of pharmaceutical forms, for increasing the dissolution rate of the drug and hence the bioavailability. They are also used in the formulation of substances with modified or target drug release into a specific tissue. Methods of thermal analysis (Thermogravimetry - TGA, Differential Scanning Calorimetry - DSC and Thermal microscopy - TM), spectroscopic methods (Infrared Spectroscopy - IR, especially Fourier Transform Infrared Spectroscopy - FTIR and Raman spectroscopy), crystallographic methods (Powder X-Ray Diffraction - PXRD) and finally Scanning Electron Microscopy (SEM) are the most powerful in the characterization of modern therapeutic systems with porous adsorbents. The problem-solving power of each particular analytical method is often enhanced by using simultaneous methods rather than a single technique.

Cancer is a widespread disease characterized by high mortality. To improve the survival rate or facilitate effective therapy, accurate and reliable diagnosis at an early stage is needed. For this reason, there is a continuous push to develop sensitive methods which can be used in cancer diagnosis. Current diagnosis relies on the quantification of cancer biomarkers defined as molecules that are measurable in body fluids or tissues and indicate a change in physiological processes with subsequent pathological manifestations. This contribution reviews recent developments in the area of electrochemical immunosensors applicable for the detection of cancer biomarkers that occur in a wide concentration range including extremely low levels, which are typical for the early stage of the disease. A summary of various antibody labels used for biomarker analysis and combined with electrochemical detection is presented. The potential of multiple biomarker analysis, with its indisputable clinical impact for accurate diagnosis, is also highlighted.

Nowadays in biosensing, development of analytical techniques is focused on improvement for monitoring biologically active species in living organisms, especially in real-time analysis. This article provides an overview of applications of electrochemical tyrosinase biosensors in the analysis of medicinally significant substances, also known as biomarkers. At the beginning, special attention is paid to characterisation of the tyrosinase enzyme, explanation of reaction mechanisms of tyrosinase with various types of electrochemical transducers and techniques needed for stable immobilization of this biocatalyst on the transducer surface used. In this case, amperometric transducers represent the most frequently used type of electrochemical sensing because they usually provide sensitive current response to the presence of analyte in the sample. Many scientific works suggest that these very selective bioanalytical devices could find application in the clinical diagnosis of various serious diseases because they represent the effective analytical tools for diagnosis of neurodegenerative disorders, detection of microbial pathogens responsible for foodborne illness and diagnosis of cytopathology, especially melanoma cancer. Additionally, various kinds of electrochemical tyrosinase biosensors are presented which were developed to determine the catalytic activity of other enzymes significant for human metabolism, medicaments and their metabolic products, several hormones, amino acids and proteins. Despite all of their advantages, it is necessary to state that tyrosinase biosensors are still not used in the routine laboratory practice due to their relatively short service life which is not longer than one month unfortunately. Never-ending development of catalytic polymers imitating the tyrosinase active site could be one of ways to solve this serious drawback.

In order to replace bio-macromolecules by stable synthetic materials in separation techniques and bioanalysis biomimetic receptors and catalysts have been developed: Functional monomers are polymerized together with the target analyte and after template removal cavities are formed in the “molecularly imprinted polymer” (MIP) which resemble the active sites of antibodies and enzymes. Starting almost 80 years ago, around 1,100 papers on MIPs were published in 2016. Electropolymerization allows to deposit MIPs directly on voltammetric electrodes or chips for quartz crystal microbalance (QCM) and surface plasmon resonance (SPR). For the readout of MIPs for drugs amperometry, differential pulse voltammetry (DPV) and impedance spectroscopy (EIS) offer higher sensitivity as compared with QCM or SPR. Application of simple electrochemical devices allows both the reproducible preparation of MIP sensors, but also the sensitive signal generation. Electrochemical MIP-sensors for the whole arsenal of drugs, e.g. the most frequently used analgesics, antibiotics and anticancer drugs have been presented in literature and tested under laboratory conditions. These biomimetic sensors typically have measuring ranges covering the lower nano- up to millimolar concentration range and they are stable under extreme pH and in organic solvents like nonaqueous extracts.

After oral administration, drug absorption from solid dosage forms depends on the release of the drug active compounds from the dosage form, the dissolution or solubilization of the drug under physiological conditions, and the permeability across the gastrointestinal tract. Dissolution testing is an essential part of designing more effective solid dosage forms in pharmaceutical industry. Moreover, dissolution testing contributes to the selection of appropriate formulation excipients for improving the dosage form efficiency. This study aims to analyze in-vitro drug dissolution testing in solid dosage forms since 2010 in order to present a comprehensive outlook of recent trends. In doing that the previous studies in the literature are summarized in the form of a table to demonstrate the apparatuses used for dissolution testing, the media in which the solid dosage form is dissolved, the method preferred for analysis from dissolution media, the conditions of analyses and the results obtained.

Testosterone is the principal endogenous androgenic–anabolic steroid in humans. The levels of testosterone in the human body are correlated with many hormonal disorders (hypogonadism, impotence, etc) mostly in men, and with many types of diseases such as: prostate cancer, metabolic syndrome, obesity, cardiovascular diseases and so on. Testosterone is extensively used among sportsmen willing to increase strength, aggressiveness, and recovery; making it the most commonly reported substance in steroid abuse. Fast, easy and cheap methods for the evaluation of testosterone are extremely needed in clinics and hospitals. This review is dedicated to surveying recent determination methods of testosterone from different biological samples such as: serum, saliva, plasma, urine or fingernail samples. After a brief description of the role of this steroid hormone in the biomedical field, various types of determination methods are described. The most important methods are immunoassays, liquid chromatography tandem massspectrometry and electrochemical methods. Different types of sensors were designed for the rapid assessment of testosterone: immunosensors, biosensors, stochastic or multimode sensors. One can conclude that to date, the available methods of analysis can cover a wide concentration range, able to detect testosterone from children`s saliva, where the levels are the lowest (using stochastic sensors), to whole blood, where electrochemical, immunological and chromatographic methods can be used.

Liquid chromatography (LC) coupled to an electrochemical (EC) detector is a complementary analytical tool compared to LC coupled with optical or mass spectrometry detectors (LC-MS). LC-EC can be applied to the determination of molecules difficult to be analyzed by other commercially available detectors. New EC detector design and new working electrode material have extended the scope of application in the field of pharmaceutical compounds analysis. Combining EC with LC-MS offers additional advantages compared to optical detectors in terms of drug stability and drug metabolism mimicry studies. Selected literature devoted to pharmacologically active compounds in their dosage forms, herbal drugs in natural products, drug residues in feed and/or in biological samples are reported in this review.

Alzheimer's disease (AD) is a widespread form of dementia that is estimated to affect 44.4 million people worldwide. AD pathology is closely related to the accumulation of amyloid beta (Aβ) peptides in fibrils and plagues, the small oligomeric intermediate species formed during the Aβ peptides aggregation presenting the highest neurotoxicity. This review discusses the recent advances on the Aβ peptides electrochemical characterization. The Aβ peptides oxidation at a glassy carbon electrode occurs in one or two steps, depending on the amino acid sequence, length and content. The first electron transfer reaction corresponds to the tyrosine Tyr10 amino acid residue oxidation, and the second to all three histidine (His6, His13 and His14) and one methionine (Met35) amino acid residues. The Aβ peptides aggregation and amyloid fibril formation are electrochemically detected via the electroactive amino acids oxidation peak currents decrease that occurs in a time dependent manner. The Aβ peptides redox behaviour is correlated with changes in the adsorption morphology from initially random coiled structures, corresponding to the Aβ peptide monomers in random coil or in α-helix conformations, to aggregates, protofibrils and two types of fibrils, corresponding to the Aβ peptides in a β-sheet configuration, observed by atomic force microscopy. Electrochemical studies of Aβ peptides aggregation, mediated by the interaction with metal ions, particularly zinc, copper and iron, and different methodologies concerning the detection of Aβ peptide biomarkers of AD in biological fluids, using electrochemical biosensors, are also discussed.

Background: Latest data from International Agency for Cancer Research shows that breast cancer is the leading cancer site in women and is the leading cause of death among female cancers. Induction of reactive oxygen species (ROS) and oxidative stress as a consequence of impaired balance between prooxidants and antioxidants are suggested to be involved in induction and progression of breast cancer. Cancer cells are found to exhibit higher levels of ROS compared to normal cells. However increased antioxidant defence which balances the oxidative status within the cancer cells suggests that high ROS levels may prevent tumorigenesis via various mechanisms. These contradictory roles of ROS and oxidative stress in breast cancer let scientists investigate potential oxidative stress modulators as anticancer strategies. Conclusions: In the present review we address the mechanisms of ROS production in breast cancer cells, the role of impaired oxidative status as well as the benefits of introducing oxidative stress modulators in therapeutic strategies in breast cancer. This review is focusing more on melatonin which we have been working on during the last decade. Our data, in accordance with the literature, suggest an important role for melatonin in breast cancer prevention and adjuvant therapy.

Background: Studies on the interactions of DNA with small molecular drugs are currently performed both to explore their mechanism of action and to develop new drugs. Electrochemical biosensors offer a very promising alternative to more complex conventional techniques for drug determination due to rapidness, low cost, simplicity, high sensitivity and compatibility with use in different settings. In this review, selected electrochemical nucleic acid-based biosensing methods described so far for the determination of pharmaceuticals and illicit drugs are briefly overviewed, discussing their basics and main features. A section pointing out general conclusions and future directions in this field is also provided. Results: The 42 selected contributions described electrochemical platforms to determine drugs of interest by monitoring their specific interactions with nucleic acids (DNA and aptamers), DNA damage and specific DNA-protein interactions. The highlighted approaches reported the use of electrodes unmodified or modified with nanomaterials and/or polymers in which DNA-drug interaction was followed by electrochemical detection of DNA puric bases, active drug or diffusion-free markers, and monitoring changes in the surface layer morphology/permeability and charge transfer resistance using different electrochemical techniques. Conclusion: Although electrochemical nucleic acid biosensing approaches constitute an interesting option for drugs determination in terms of cost, simplicity and miniaturized instrumentation, validating exhaustively their performance in real samples against conventional methodologies and implementing them into portable and automatic high throughput devices, together with exploring novel electrode modifications with nanomaterials and polymers and studying in more detail their multiplexing ability for analysis of a large number of analytes, is still needed.

Background: The detection of biological molecules referred as biomarkers in biological fluids is fundamental in clinical analysis because it permits to discriminate between healthy and ill individuals and to evaluate the progress of a disease. The development of immunosensors for the detection and monitoring of biomarkers is currently a major area of research and, as more markers are discovered and their role in disease becomes better understood, this will continue to grow. Methods: We report the research progresses of electrochemical immunosensor applied in clinical analysis that have been published in the last three years. Results: The emphasis of this review is on the advances of the electrochemical immunosensors for detection and monitoring of cancerous, cardiovascular and neurological diseases. An immunosensor overview was presented as well as the biomarkers and biosensing systems currently used to detect the onset and monitor the progression of the mentioned diseases. Conclusions: Electrochemical biosensors focusing on a vast repertoire of analytes are now becoming one of the most widely explored scientific fields. This is due to their enormous potential in clinical diagnosis and biological process monitoring. In the near future, with the development of transducer technology, nano-sized material technology, and biomolecules engineering technology, biosensors should be powerful tools in several analytical areas.

The features and applications of silver amalgam electrodes in electroanalysis of pharmaceuticals and vitamins are summarized in this review. The state-of-the-art in the preparation and construction of solid silver amalgam electrodes for prolonged and userfriendly use is presented. Although not as widely spread as other electrode materials, silver amalgam possesses a unique and viable combination of favorable electrochemical properties, which are close to ideal mercury electrodes, non-toxic character, high durability and mechanical stability, if properly prepared. Its capability of conducting the redox processes at highly negative potentials is essential for the analysis of large number of bioactive organic compounds. The review features also overview information for each application in drug or vitamin analysis divided to the sections according to the construction variants of silver amalgam electrodes.

While the amino acids, enzymes and hormones are chiral, chirality plays significant role in the life of plants, animals, as well as the human being. Chirality of molecules is important in various industries, such as pharmaceutical, agricultural, food, electronics, etc. Chiral drugs may have different bioavailability, distribution, biotransformation and excretion, as well as quantitatively and/or qualitatively different pharmacological or toxic properties. Enantiomerically pure chiral drugs have been increasingly developed for the pharmaceutical market due to their superiority from the viewpoints of potency and safety. This is supported by the development of new methods for enantioselective production of the chiral compounds, as well as by the capability of the enantioselective analytical methods to allow a detection and quantification of minor enantiomeric impurity in the presence of another enantiomer in a large excess. The aim of the present review is to provide a short summary of the basic principles of chiral separations on an analytical and preparative scale. In addition, some selected applications for analytical techniques, such as gas chromatography, supercritical fluid chromatography, high performance liquid chromatography, capillary electrophoresis and capillary electrochromatography for the separation of enantiomers of chiral pharmaceuticals published in the last two years are also discussed.