Ionic liquids: A pharmaceutical perspective

In the last decades, ionic liquids (ILs) progressed from chemical curiosities to interesting biological compounds apprehending the attention of researchers of distinct areas, from chemistry to pharmacology. Initially, ILs were explored as materials for diverse applications due to the possibility of synthesize compounds with targeted chemical properties combined with selected physical properties. More recently, the emergence of ILs with biological activity revolutionized the scientific focus of these compounds and opened interesting perspectives regarding their pharmaceutical application. From the pharmaceutical point of view, an IL approach, in the design of novel active pharmaceutical ingredients (APIs), appears to be appropriate as it enables the chemical manipulation of the compounds with specific objectives related with the manufacturing process, the stability of the formulation, bioavailability and eventual adverse effects. Furthermore, even though crystallinity confers advantages during isolation, processing and storage of the drug, it is known that solid forms of APIs often suffer from low solubility and polymorphic conversion which can influence negatively the bioavailability of the drug and ultimately its therapeutic effect. On a distinct perspective, the possibility of engineering the properties of ILs by manipulating anion-cation combinations, in association with their solvent properties and in some cases water-miscibility, are considered promising characteristics regarding the applicability of ILs as solvents or carriers of pharmaceutical drugs. In this chapter it is intended to expose the pharmaceutical potential of ILs through the discussion of their utilization either as APIs or solvents/carriers of pharmaceutical drugs. The discussion will be centered on the benefits of the IL approach for the development of novel drug candidates considering not only physico-chemical aspects but also the pharmaceutical profile of the developed active pharmaceutical ingredients with IL properties. Considering the utilization of ILs as solvents of drugs or as part of drug delivery systems, it is anticipated that the discussion will be focused on the efficiency and toxicity of the systems and on their influence on the pharmacokinetics and pharmacodynamics of the vehiculated drugs. It is also planned to debate the motivations for the pharmaceutical usage of ILs as well as their peculiar properties that launched them in this context. Currently, the pharmaceutical utilization of ILs is one of the most relevant applications of these solvents, with impact on the safety and effectiveness of the involved processes and with benefits in terms of pharmaceutical formulations and pharmacological activity. It is our belief that this chapter is adequate for the book in project and can greatly enhance its acceptance and interest by readers in distinct research areas

Manual or automated measuring of antipsychotics chemical oxygen demand

Antipsychotic (AP) drugs are becoming accumulated in terrestrial and aqueous resources due to their actual consumption. Thus, the search of methods for assessing the contamination load of these drugs is mandatory. The COD is a key parameter used for monitoring water quality upon the assessment of the effect of polluting agents on the oxygen level. Thus, the present work aims to assess the chemical oxygen demand (COD) levels of several typical and atypical antipsychotic drugs in order to obtain structure-activity relationships. It was implemented the titrimetric method with potassium dichromate as oxidant and a digestion step of 2 h, followed by the measurement of remained unreduced dichromate by titration. After that, an automated sequential injection analysis (SIA) method was, also, used aiming to overcome some drawbacks of the titrimetric method. The results obtained showed a relationship between the chemical structures of antipsychotic drugs and their COD values, where the presence of aromatic rings and oxidable groups give higher COD values. It was obtained a good compliance between the results of the reference batch procedure and the SIA system, and the APs were clustered in two groups, with the values ratio between the methodologies, of 2 or 4, in the case of lower or higher COD values, respectively. The SIA methodology is capable of operating as a screening method, in any stage of a synthetic process, being also more environmentally friendly, and cost-effective. Besides, the studies presented open promising perspectives for the improvement of the effectiveness of pharmaceutical removal from the waste effluents, by assessing COD values

Determination of metoprolol, acebutolol and propranolol in pharmaceutical formulations using the same SIA system

A mechanized system for the determination of beta-blockers in pharmaceutical formulations is presented. Using the Sequential Injection Analysis (SIA) technique it was achieved a simple, economical and versatile methodology adaptable to any pharmaceutical control involving these substances. It does not require any pre-treatment for the samples, as they must only be dissolved in acid before analysis. Linear calibration plots were obtained for metoprolol (40.52 - 250 mg L-1), acebutolol (32.85 - 140 mg L-1) and propranolol (16.58 - 120 mg L-1). A R.S.D. lower than 5% was attained. The methodology was used in tablets, injections and prolonged-release capsules. Common excipients used in pharmaceuticals do not interfere. Statistical comparison of the results obtained with the proposed methodology and with the official methods showed good agreement (95% confidence level). SIA system produces only 2.50 mL of effluents per determination whereas the reference methodologies consume around 140 mL

Nanoparticle-based assays in automated flow systems: A review

Nanoparticles (NPs) exhibit a number of distinctive and entrancing properties that explain their ever increasing application in analytical chemistry, mainly as chemosensors, signaling tags, catalysts, analytical signal enhancers, reactive species generators, analyte recognition and scavenging/separation entities. The prospect of associating NPs with automated flow-based analytical is undoubtedly a challenging perspective as it would permit confined, cost-effective and reliable analysis, within a shorter timeframe, while exploiting the features of NPs. This article aims at examining state-of-the-art on continuous flow analysis and microfluidic approaches involving NPs such as noble metals (gold and silver), magnetic materials, carbon, silica or quantum dots. Emphasis is devoted to NP format, main practical achievements and fields of application. In this context, the functionalization of NPs with distinct chemical species and ligands is debated in what concerns the motivations and strengths of developed approaches. The utilization of NPs to improve detector's performance in electrochemical application is out of the scope of this review. The works discussed in this review were published in the period of time comprised between the years 2000 and 2013

Automatic miniaturized flow methodology with in-line solid-phase extraction for quinine determination in biological samples

The present work describes an analytical platform based on a multipumping flow injection analysis (MPFS) technique combined with in-line solid-phase extraction (SPE). The flow network has been tested with the determination of quinine in biological samples using fluorometry as the detection technique. Amberlite XAD-4 resin has been used as a solid phase and the implementation of a pH control strategy resulted in a simple and environmental approach for the preconcentration of quinine. Two solenoid valves allowed the deviation of the flow towards the resin column to carry out SPE procedures. The influence of parameters such as concentration, flow rate and volume of the different solutions on the sensitivity and performance of the MPFS was studied. Dynamic calibration ranges (0.78–150 ng mL 1) for quinine determination were applied by using a variable sample volume (120– 1000 mL). The developed methodology provided high relative extraction recoveries from human urine samples (85–115%). The proposed automatic methodology turns out to be very efficient and sustainable compared to the available procedures and it could prove to be an attractive alternative tool to perform in-line sample pre-treatment and subsequent direct determination of relevant organic compounds in pharmaceutical and clinical analyses

Multicommuted flow system for the determination of glucose in animal blood serum exploiting enzymatic reaction and chemiluminescence detection

An automatic flow procedure based on multicommutation dedicated for the determination of glucose in animal blood serum using glucose oxidase with chemiluminescence detection is described. The flow manifold consisted of a set of three-way solenoid valves assembled to implement multicommutation. A microcomputer furnished with an electronic interface and software written in Quick BASIC 4.5 controlled the manifold and performed data acquisition. Glucose oxidase was immobilized on porous silica beads (glass aminopropyl) and packed in a minicolumn (15 × 5 mm). The procedure was based on the enzymatic degradation of glucose, producing hydrogen peroxide, which oxidized luminol in the presence of hexacyanoferrate(III), causing the chemiluminescence. The system was tested by analysing a set of serum animal samples without previous treatment. Results were in agreement with those obtained with the conventional method (LABTEST Kit) at the 95% confidence level. The detection limit and variation coefficient were estimated as 12.0 mg l(−1) (99.7% confidence level) and 3.5% (n = 20), respectively. The sampling rate was about 60 determinations h(−1) with sample concentrations ranging from 50 to 600 mg l(−1) glucose. The consumptions of serum sample, hexacyanoferrate(III) and luminol were 46 μl, 10.0 mg and 0.2 mg/determination, respectively

Anti-inflamatório choline based ionic liquids: Insights into their lipophilicity, solubility and toxicity parameters

The impact on in vivo efficacy and safety of two novel ionic liquids based on the association of choline with nonsteroidal anti-inflammatory drugs, ketoprofen and naproxen forming IL-APIs, was evaluated. Their lipophilicity, solubility and toxicity were assessed aiming the illustration of the pharmaceutical profile and potential toxic impact. Partition coefficientwas determined usingmicelles of hexadecylphosphocholine and UV–Vis derivative spectroscopy. Additionally, solubility in phosphate buffer pH 7.4 wasmeasured using amodified shake flaskmethod and UV–Vis spectroscopy as detection technique. Ultimately, toxicity was considered resorting to a fully automated cytochrome c oxidase assay based onmicrofluidics. The obtained results demonstrated that the IL-APIs' drug format has the ability to interact with biological membranes and also improves solubility up to 58 times. Moreover, it was evidenced that, although being a nutrient, choline influences the IL-APIs' toxicity. The studied anti-inflammatory IL-APIs exhibited promising properties regarding their incorporation in pharmaceutical formulations

Combined use of phosphonium-erythrosin B-based nanoGUMBOS, UV–Vis spectroscopy, and chemometrics for discrimination and quantification of proteins

Nanoparticles derived from a group of uniform materials based on organic salts (nanoGUMBOS) are considered promising candidates for protein analysis due to their facile synthesis in aqueous media and high tunability. In this study, a phosphonium-erythrosin B-based nanoGUMBOS (i.e., [P4444]2[EB]) was prepared using an ultrasound-assisted reprecipitation method, and its ability to discriminate and quantify proteins was evaluated. Sonication time (30 s, 5 min, and 15 min) and cyclodextrin templating (α-, 2-HP-β-, and γ-CD) were investigated for their effects on discrimination performance of synthesized nanomaterial. Six proteins (albumin, hemoglobin, trypsin, catalase, lysozyme, and cytochrome c) with different abundance levels and physicochemical properties were selected as target analytes. Absorbance response patterns generated from interactions between [P4444]2[EB] nanoGUMBOS and proteins were analyzed using partial least squares discriminant analysis. Percentages of correct protein discrimination ranged from 94.6 to 99.6%, with the latter being the best result obtained using non-templated nanoGUMBOS formed after 5 min sonication. Under optimized conditions, it was possible to discriminate all protein samples with percentages of correct assignments greater than 90% for concentrations as low as 2.0 μg mL−1. The discrimination capability of synthesized nanoGUMBOS was further evaluated using mixtures of different ratios of lysozyme, cytochrome c, and hemoglobin. Finally, partial least squares models were developed for protein quantification and the best performance was observed for albumin. Results support potential use of [P4444]2[EB] nanoGUMBOS in combination with ultraviolet–visible spectroscopy and chemometrics for qualitative and quantitative analyses of individual proteins and mixtures of proteins.info:eu-repo/semantics/publishedVersio

The inhibitory capacity of organometallic compounds with anticancer features in GST P1-1 enzyme activity: An automatic approach

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Anti-inflammatory choline based ionic liquids: Insights into their lipophilicity, solubility and toxicity parametrites

The impact on in vivo efficacy and safety of two novel ionic liquids based on the association of choline with nonsteroidal anti-inflammatory drugs, ketoprofen and naproxen forming IL-APIs, was evaluated. Their lipophilicity, solubility and toxicity were assessed aiming the illustration of the pharmaceutical profile and potential toxic impact. Partition coefficientwas determined usingmicelles of hexadecylphosphocholine and UV–Vis derivative spectroscopy. Additionally, solubility in phosphate buffer pH 7.4 wasmeasured using amodified shake flaskmethod and UV–Vis spectroscopy as detection technique. Ultimately, toxicity was considered resorting to a fully automated cytochrome c oxidase assay based onmicrofluidics. The obtained results demonstrated that the IL-APIs' drug format has the ability to interact with biological membranes and also improves solubility up to 58 times. Moreover, it was evidenced that, although being a nutrient, choline influences the IL-APIs' toxicity. The studied anti-inflammatory IL-APIs exhibited promising properties regarding their incorporation in pharmaceutical formulations