Current Pharmaceutical Analysis - Volume 17, Issue 3, 2021

In this review paper, miniaturized techniques, including both electromigration and liquid chromatographic techniques, have been discussed considering their main features in the analytical field for the separation and analysis of Nonsteroidal Anti-inflammatory Drugs (NSAIDs). In Capillary Electrophoresis (CE) and nano-liquid chromatography (nano-LC), separation is performed in capillaries with Internal Diameter (I.D.) lower than 100 μm and therefore flow rates in the range 100-1000 nL/min are applied. Therefore, due to the low flow rate, high mass sensitivity can be obtained. Usually, conventional UV detectors are used on-line; however, these techniques can be coupled with Mass Spectrometry (MS). CE and nano-LC have also been applied to the separation of NSAIDs using silica stationary phases (SP) modified with C18 promoting interaction with analytes mainly based on hydrophobic interaction. Besides, the use of chiral SP was found to be effective for the chiral resolution of these compounds. In addition to silica phases, monolithic (both organic and inorganic) material has also been used. Although most of the presented studies aimed to demonstrate the usefulness of the considered microfluidic techniques, some applications to real samples have also been reported.

Background: Significant advances have been occurred in analytical research since the 1970s by Liquid Chromatography (LC) as the separation method. Reverse Phase Liquid Chromatography (RPLC) method, using hydrophobic stationary phases and polar mobile phases, is the most commonly used chromatographic method. However, it is difficult to analyze some polar compounds with this method. Another separation method is the Normal Phase Liquid Chromatography (NPLC), which involves polar stationary phases with organic eluents. NPLC presents low-efficiency separations and asymmetric chromatographic peak shapes when analyzing polar compounds. Hydrophilic Interaction Liquid Chromatography (HILIC) is an interesting and promising alternative method for the analysis of polar compounds. HILIC is defined as a separation method that combines stationary phases used in the NPLC method and mobile phases used in the RPLC method. HILIC can be successfully applied to all types of liquid chromatographic separations such as pharmaceutical compounds, small molecules, metabolites, drugs of abuse, carbohydrates, toxins, oligosaccharides, peptides, amino acids and proteins. Objective: This paper provides a general overview of the recent application of HILIC in the pharmaceutical research in the different sample matrices such as pharmaceutical dosage form, plasma, serum, environmental samples, animal origin samples, plant origin samples, etc. Also, this review focuses on the most recent and selected papers in the drug research from 2009 to the submission date in 2020, dealing with the analysis of different components using HILIC. Results and Conclusion: The literature survey showed that HILIC applications are increasing every year in pharmaceutical research. It was found that HILIC allows simultaneous analysis of many compounds using different detectors.

Albumin is an ideal material for the production of drug carrier nanoparticular systems since it is a versatile and functional protein that has been proven to be biodegradable and biocompatible, non-toxic, and immunogenic. Albumin nanoparticles are of great interest as they have the high binding capacity to many drugs with different physicochemical and structural properties and are well tolerated without any side effects. In this review, different types of albumin, special nanotechnological techniques for the production of albumin nanoparticles, such as desolvation, emulsification, thermal gelation, nano-spray drying, and self-assembly, as well as the characterization of albumin nanoparticles, such as particle size, surface charge, morphological properties, drug content, and release profile have been discussed. In addition, the in vitro and in vivo studies of albumin nanoparticles intended both diagnostic and therapeutic usage have been investigated.

The content and the application of pharmaceutical dosage forms must meet several basic requirements to ensure and maintain efficiency, safety and quality. A large number of active substances have a limited ability to direct administration. Excipients are generally used to overcome the limitation of direct administration of these active substances. However, the function, behavior and composition of the excipients need to be well known in the design, development and production of pharmaceutical dosage forms. In this review, excipients used to assist in any pharmaceutical dosage form production processes of drugs, to preserve, promote or increase stability, bioavailability and patient compliance, to assist in product identification/separation, or to enhance overall safety and effectiveness of the drug delivery system during storage or use are explained. Moreover, the use of these excipients in drug delivery systems is identified. Excipient toxicity, which is an issue discussed in the light of current studies, also discussed in this review.

One of the major developments of the last decade is the preparation of in situ implant formulations. Injectable, biocompatible and/or biodegradable polymer-based in situ implants are classified differently due to implant formation based on in vivo solid depot or formation mechanisms inducing liquid form, gel or solid depot. In this review, published studies to date regarding in situ forming implant systems were compiled and their formation mechanisms, materials and methods used, routes of administration, chemical and analytical characterizations, quality-control tests and In vitro dissolution tests were compared in Tables and were evaluated. There are several advantages and disadvantages of these dosage forms due to the formation mechanism, polymer and solvent type and the ratio used in formulations and all of these parameters have been discussed separately. In addition, new generation systems developed to overcome the difficulties encountered in in situ implants have been evaluated. There are some approved products of in situ implant preparations that can be used for different indications available on the market and the clinical phase studies nowadays. In vitro and in vivo data obtained by the analysis of the application of new technologies in many studies evaluated in this review showed that the number of approved drugs to be used for various indications would increase in the future.

Background: The Human Immunodeficiency Virus (HIV) has now been established as the causative agent of the Acquired Immunodeficiency Syndrome (AIDS) and exactly 25 antiretroviral drugs have been formally approved for clinical use in the treatment of AIDS. The life quality and duration of HIV-positive patients have increased with the usage of antiretroviral drugs in the treatment of AIDS. Nucleoside Reverse Transcriptase Inhibitors (NRTIs) are one of the subgroups of antiretroviral. Objective: The quantification of drugs is important, as they make positive contributions to dose adjustments in practice. Voltammetric methods are very powerful analytical methods used in the pharmaceutical industry because of the determination of therapeutic agents and/or their metabolites in clinical samples at extremely low concentrations (10-50 ng/ml). Methods: This review mainly includes the pharmacological properties and recent determination studies by voltammetric methods from pharmaceutical dosage forms and biological samples of eight NRTIs group antiretroviral drugs (zidovudine, abacavir, adefovir, entecavir, zalcitabine, didanosine, emtricitabine, lamivudine) that are used in the clinic and show electroactive properties, were performed. Conclusion: Due to the variety of working electrodes in voltammetric methods, it is possible to choose the electrode that best responds. In this way, the analysis of NRTIs was possible at lower concentrations in pharmaceuticals and biological samples with voltammetric methods in these studies without the necessity for the sample pre-treatment or time-consuming extraction steps. The voltammetric methods provide good stability, repeatability, reproducibility and high recovery for the analysis of the analyte. They could be used for the pharmacokinetic studies as well as for quality control laboratory studies.

The electrochemical analysis offers a number of important advantages such as providing information on pharmaceuticals analysis and their in vivo redox processes and pharmacological activity. The interest in developing electrochemical sensing devices for use in clinical assays is growing rapidly. Metallic nanoparticles can be synthesized and modified with various chemical functional groups, which allow them to be conjugated with antibodies, ligands, and drugs of interest. In this article, the novel developments to enhance the performance of sensor modified with metal nanoparticles of pharmaceuticals were reviewed. A discussion of the properties of metal nanostructures and their application in drug analysis is presented. Their application as a modifier agent in determining low levels of drugs in pharmaceutical dosage forms and biological samples is discussed. It has been found that the electrocatalytic effect of the electrode, sensitivity and selectivity were increased using various working electrodes modified with nano-sized metal, metal oxide and metal/metal oxide particles.

Analysis of pharmaceutical products, as well as their active and inactive ingredients, and identification and characterization of potential impurities originating from raw materials and manufacturing processes is of importance in the field, especially for further assessment of potential positive or negative effects on the human body. In addition to expected therapeutic effects, unfortunately, some unwanted or adverse effects were encountered in the past, resulting in dramatic cases sometimes. These challenges have been overcome with the use of sophisticated and high-end analytical techniques today by focusing on developing more efficient, more accurate, more accessible, and faster determination techniques. One of the powerful techniques utilized under the given aim, especially for qualitative purposes, is the Time of Flight (TOF) based Mass Spectrometry (MS). Among the TOF-MS instruments, liquid chromatography- mass spectrometry-ion trap-time of flight (LCMS-IT-TOF) has a unique MSⁿ capability, which is a versatile tool in exact mass prediction and structure elucidation. In this review, LCMS-ITTOF has been considered taking all aspects to account for its use in qualitative impurity profiling, and a retrospective view on previous studies was presented in an analytical manner.

Background: Biomarkers are very important disease-related biomolecules which should be analyzed sensitive and selective in related physiological fluids or tissues. Tumor necrosis factor-α is a type of cytokine which plays vitlly important roles in different methabolic pathways such as cell death, survival, differentiation, proliferation and migration, and infectious and inflammatory diseases including rheumatoid arthritis, diabetes. Objective: In this study, it was aimed to develop a reliable tool based on star-shaped poly(glycidyl methacrylate) polymer coated disposable indium tin oxide electrode for determination of Tumor necrosis factor-α, an important disease biomarker. Methods: Star shaped polymer was used as an interface material for anti- Tumor necrosis factor α antibodies immobilization. The antibodies were immobilized covalently onto polymer coated indium tin oxide electrode. Electrochemical impedance spectroscopy and cyclic voltammetry techniques were used for all electrochemical measurements. Results: The suggested immunosensor exhibited a linear range between 0.02 and 4 pg/mL Tumor necrosis factor-α, and the detection limit was found as 6 fg/mL. Scanning electron microscopy and atomic force microscopy were used for electrode surface characterization. In addition, the suggested immunosensor was used for Tumor necrosis factor-α sensing in human serum samples. The results displayed recoveries between 97.07 and 100.19%. Moreover, this immunosensor had a simple fabrication procedure and a long storage-stability. Conclusion: A new biosensor based on a Star shaped polymer for the ultra sensitive determination of a biomarker Tumor necrosis factor-α was developed. The biosensor presented excellent repeatability and reproducubility, and also wide calibration range for Tumor necrosis factor- α