Applications of metal organic frameworks in dispersive micro solid phase extraction (D-µ-SPE).

Metal-organic frameworks (MOFs) are a fascinating family of crystalline porous materials made up of metal clusters and organic linkers. In comparison with other porous materials, MOFs have unique characteristics including high surface area, homogeneous open cavities, and permanent high porosity with variable shapes and sizes. For these reasons, MOFs have recently been explored as sorbents in sample preparation by solid-phase extraction (SPE). However, SPE requires large amounts of sorbents and suffers from limited contact surfaces with analytes, which compromises extraction recovery and efficiency. Dispersive SPE (D-SPE) overcomes these limitations by dispersing the sorbents into the sample, which in turn increases contact with the analytes. Miniaturization of the microextraction procedure, particularly the amount of sorbent reduces the amount consumed of the organic solvent and shorten the time required to attain the equilibrium state. This may explain the reported high efficiency and applicability of MOFs in dispersive micro SPE (D-µ-SPE). This method retains all the advantages of solid phase extraction while also being simpler, faster, cheaper, and, in some cases, more effective in comparison with D-SPE. Besides, D-µ-SPE requires smaller amounts of the sorbents which reduces the overall cost, and the amount of waste generated from the analytical process. In this review, we discuss the applications of MOFs in D-µ-SPE of various analytes including pharmaceuticals, pesticides, organic dyes from miscellaneous matrices including water samples, biological samples and food samples.

Homogeneous liquid-liquid microextraction coupled with HPLC/DAD for determination of nirmatrelvir and ritonavir as COVID-19 combination therapy in human plasma.

The study reports the development of a high-performance liquid chromatography/diode array detection method to measure the levels of nirmatrelvir and ritonavir in human plasma. These two antiviral medications are used for the treatment of COVID-19 and are marketed as Paxlovid®. The method employed sugaring-out induced homogeneous liquid-liquid microextraction to improve sensitivity. Optimization of the method was performed using the one variable at a time approach by adjusting several factors such as type of sugar, extractant, amount of sugar, volume of extractant, and pH of the aqueous sample to achieve the highest efficiency. The developed method was validated according to the Food and Drug Administration guidelines and demonstrated good linearity, accuracy, and precision. The range of linearity was from 1000 to 20,000 ng/mL for nirmatrelvir and 200 to 20,000 ng/mL for ritonavir with correlation coefficient values of 0.998 and 0.996, respectively. Selectivity studies revealed that no others peaks appeared in the retention times of the studied drugs. The stability of nirmatrelvir and ritonavir were also investigated through short term and three cycles of freeze-thaw, and both drugs were found stable. This analytical method could be useful for monitoring drug concentrations in patients undergoing treatment with these medications for COVID-19. In this work, for the first time, SULLME was used for the sensitive determination of nirmatrelvir and ritonavir in biological fluids. The developed method was able to determine both drugs in therapeutic levels with no need to sophisticated techniques like LC-MS. In addition to that, SULLME is considered a simple and green sample preparation in comparison with conventional sample preparation methods.

Analytical Methods for the Determination of Quercetin and Quercetin Glycosides in Pharmaceuticals and Biological Samples.

Flavonoids are plant-derived compounds that have several health benefits, including antioxidative, anti-inflammatory, anti-mutagenic, and anti-carcinogenic effects. Quercetin is a flavonoid that is widely present in various fruits, vegetables, and drinks. Accurate determination of quercetin in different samples is of great importance for its potential health benefits. This review, is an overview of sample preparation and determination methods for quercetin in diverse matrices. Previous research on sample preparation and determination methods for quercetin are summarized, highlighting the advantages and disadvantages of each method and providing insights into recent developments in quercetin sample treatment. Various analytical techniques are discussed including spectroscopic, chromatographic, electrophoretic, and electrochemical methods for the determination of quercetin and its derivatives in different samples. UV-Vis (Ultraviolet-visible) spectrophotometry is simple and inexpensive but lacks selectivity. Chromatographic techniques (HPLC, GC) offer selectivity and sensitivity, while electrophoretic and electrochemical methods provide high resolution and low detection limits, respectively. The aim of this review is to comprehensively explore the determination methods for quercetin and quercetin glycosides in diverse matrices, with emphasis on pharmaceutical and biological samples. The review also provides a theoretical basis for method development and application for the analysis of quercetin and quercetin glycosides in real samples.

A hybrid microcrystalline cellulose/metal-organic framework for dispersive solid phase microextraction of selected pharmaceuticals: A proof-of-concept.

Solid phase microextraction (SPME) is considered simple, ecofriendly, sustainable, cost-effective and timesaving sample preparation mode in comparison with other sample preparation procedures. The researchers always try to develop new sorbents with higher surface area in comparison with other conventional sorbents aiming to enhance the extraction efficiency. In this work for the first time, a comparative study was performed between Ca-BTC MOF (1,3,5-benzenetricarboxylic acid, BTC; metal-organic framework, MOF) and a hybrid Ca-BTC-MCC MOF (microcrystalline cellulose, MCC) by using as model compounds seven drugs with different physicochemical properties. The evaluation of the extraction efficiency of both sorbents were obtained by means of an HPLC/DAD instrument configuration in reversed phase mode under isocratic elution mode. The results indicate that Ca-BTC MOF showed superior extraction efficiency than Ca-BTC-MCC MOF in the case of all analytes except nirmatrelvir and ritonavir. The results highlight that not only the surface area of adsorbents controlled the adsorption capacity, but also other factors have a role in extraction efficiency including morphology of adsorbent and physico-chemical properties of the analytes. It is worth mentioning that this is the first time that a comparative study was performed between Ca-BTC MOF and Ca-BTC-MCC MOF hybrid material.

Spectroscopic methods for COVID-19 detection and early diagnosis.

The coronavirus pandemic is a worldwide hazard that poses a threat to millions of individuals throughout the world. This pandemic is caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), which was initially identified in Wuhan, China's Hubei provincial capital, and has since spread throughout the world. According to the World Health Organization's Weekly Epidemiological Update, there were more than 250 million documented cases of coronavirus infections globally, with five million fatalities. Early detection of coronavirus does not only reduce the spread of the virus, but it also increases the chance of curing the infection. Spectroscopic techniques have been widely used in the early detection and diagnosis of COVID-19 using Raman, Infrared, mass spectrometry and fluorescence spectroscopy. In this review, the reported spectroscopic methods for COVID-19 detection were discussed with emphasis on the practical aspects, limitations and applications.

A gadolinium-based magnetic ionic liquid for supramolecular dispersive liquid-liquid microextraction followed by HPLC/UV for the determination of favipiravir in human plasma.

Favipiravir is a potential antiviral medication that has been recently licensed for Covid-19 treatment. In this work, a gadolinium-based magnetic ionic liquid was prepared and used as an extractant in dispersive liquid-liquid microextraction (DLLME) of favipiravir in human plasma. The high enriching ability of DLLME allowed the determination of favipiravir in real samples using HPLC/UV with sufficient sensitivity. The effects of several variables on extraction efficiency were investigated, including type of extractant, amount of extractant, type of disperser and disperser volume. The maximum enrichment was attained using 50 mg of the Gd-magnetic ionic liquid (MIL) and 150 µl of tetrahydrofuran. The Gd-based MIL could form a supramolecular assembly in the presence of tetrahydrofuran, which enhanced the extraction efficiency of favipiravir. The developed method was validated according to US Food and Drug Administration bioanalytical method validation guidelines. The coefficient of determination was 0.9999, for a linear concentration range of 25 to 1.0 × 105  ng/ml. The percentage recovery (accuracy) varied from 99.83 to 104.2%, with RSD values (precision) ranging from 4.07 to 11.84%. The total extraction time was about 12 min and the HPLC analysis time was 5 min. The method was simple, selective and sensitive for the determination of favipiravir in real human plasma.

Determination of favipiravir in human plasma using homogeneous liquid-liquid microextraction followed by HPLC/UV.

Background: Favipiravir is an antiviral drug that was recently approved for the management of COVID-19 infection. Aim: This work aimed to develop a new method, using sugaring-out induced homogeneous liquid-liquid microextraction followed by HPLC/UV for the determination of favipiravir in human plasma. Materials & methods: The optimum extraction conditions were attained using 500 µl of tetrahydrofuran as an extractant and 1400 mg of fructose as a phase-separating agent. Results: The developed method was validated according to the US FDA bioanalytical guidelines and was found linear in the range of 25-80,000 ng/ml with a correlation coefficient of 0.999. Conclusion: These results showed that the developed method was simple, easy, valid and adequately sensitive for determination of favipiravir in plasma for bioequivalence studies.

Menthol-assisted homogenous liquid-liquid microextraction for HPLC/UV determination of favipiravir as an antiviral for COVID-19 in human plasma.

Favipiravir is a promising antiviral agent that has been recently approved for treatment of COVID-19 infection. In this study, a menthol-assisted homogenous liquid-liquid microextraction method has been developed for favipiravir determination in human plasma using HPLC/UV. The different factors that could affect the extraction efficiency were studied, including extractant type, extractant volume, menthol amount and vortex time. The optimum extraction efficiency was achieved using 300 µL of tetrahydrofuran, 30 mg of menthol and vortexing for 1 min before centrifuging the sample for 5 min at 3467g. Addition of menthol does not only induce phase separation, but also helps to form reverse micelles to facilitate extraction. The highly polar favipiravir molecules would be incorporated into the hydrophilic core of the formed reverse micelle to be extracted by the non-polar organic extractant. The method was validated according to the FDA bioanalytical method guidelines. The developed method was found linear in the concentration range of 0.1 to 100 µg/mL with a coefficient of determination of 0.9992. The method accuracy and precision were studied by calculating the recovery (%) and the relative standard deviation (%), respectively. The recovery (%) was in the range of 97.1-103.9%, while the RSD (%) values ranged between 2.03 and 8.15 %. The developed method was successfully applied in a bioequivalence study of Flupirava® 200 mg versus Avigan® 200 mg, after a single oral dose of favipiravir administered to healthy adult volunteers. The proposed method was simple, cheap, more eco-friendly and sufficiently sensitive for biomedical application.

Homogeneous liquid-liquid extraction as an alternative sample preparation technique for biomedical analysis.

Liquid-liquid extraction is a widely used technique of sample preparation in biomedical analysis. In spite of the high pre-concentration capacities of liquid-liquid extraction, it suffers from a number of limitations including time and effort consumption, large organic solvent utilization, and poor performance in highly polar analytes. Homogeneous liquid-liquid extraction is an alternative sample preparation technique that overcomes some drawbacks of conventional liquid-liquid extraction, and allows employing greener organic solvents in sample treatment. In homogeneous liquid-liquid extraction, a homogeneous phase is formed between the aqueous sample and the water-miscible extractant, followed by chemically or physically induced phase separation. To form the homogeneous phase, aqueous samples are mixed with water-miscible organic solvents, water-immiscible solvents/cosolvents, surfactants, or smart polymers. Then, phase separation is induced chemically (adding salt, sugar, or buffer) or physically (changing temperature or pH). This mode is rapid, sustainable, and cost-effective in comparison with other sample preparation techniques. Moreover, homogeneous liquid-liquid extraction is more suitable for the extraction of delicate macromolecules such as enzymes, hormones, and proteins and it is more compatible with liquid chromatography with tandem mass spectrometry, which is a vital technique in metabolomics and proteomics. In this review, the principle, types, applications, automation, and technical aspects of homogeneous liquid-liquid extraction are discussed.

Sugaring-out induced homogeneous liquid-liquid microextraction as an alternative mode for biological sample preparation: A comparative study.

Miniaturization of liquid-liquid extraction is a growing field of sample preparation to reduce solvent consumption, protect the environment, and preserve operators' health. In this work, four different modes of liquid-liquid microextraction have been compared including dispersive liquid-liquid microextraction, binary and ternary salting-out, and sugaring-out induced liquid-liquid microextraction. The extraction efficiency was evaluated by the enrichment factors of 14 different drugs from three pharmacological classes. Compared with the other modes, sugaring-out induced liquid-liquid microextraction was found to be the most efficient and, thus, it was applied for sample preparation of the antivirals in human plasma. Method optimization was performed using response surface methodology for the sugar type and amount (in mg), the sample pH, the equilibration time (in min), and the extractant volume (in µL). The method was then validated and found linear in the concentration range of 0.10-10 µg/mL for daclatasvir, 0.05-10 µg/mL for velpatasvir, and 0.20-10 µg/mL for ledipasvir, with correlation coefficients in the range 0.996-0.999. These results shows that sugaring-out induced liquid-liquid microextraction could be a more efficient microextraction mode for preparation of biological samples. Compared with other types of microextraction, sugaring-out induced liquid-liquid microextraction is greener, simpler, and cost-effective, with less tendency to affect the sample pH.

Salting-out induced liquid-liquid microextraction for alogliptin benzoate determination in human plasma by HPLC/UV.

Salting-out induced liquid-liquid microextraction method has been developed for plasma sample treatment before determination of alogliptin by high performance liquid chromatography with UV detection. Several parameters were optimized to achieve maximum enrichment, including type of extractant, volume of extractant, type of anion, type of cation, salt amount and pH. The optimum conditions were attained using 500 µL of acetonitrile, added to 1 mL of aqueous sample containing 250 mg of sodium chloride at pH 12. An RP-HPLC method was developed and validated according to the International Conference on Harmonization guidelines M10. The method was linear in the concentration range of 0.1 to 50 µg/mL (correlation coefficient = 0.997). The limit of detection was 0.019 µg/mL and limit of quantitation was 0.06 µg/mL. The method was accurate and precise with an average % recovery of 99.7% and a % relative standard deviation ranging between 1.5 and 2.5. These results showed that the salting-out induced liquid-liquid microextraction methods could be better than other sample preparation protocols in terms of sensitivity, easiness, solvent consumption and waste reduction.

Insights into the FDA 2018 New Drug Approvals.

OBJECTIVE: The Center of Drug Evaluation and Research (CDER) in the food and drug administration (FDA) approves new drugs every year. This review discusses the novel drugs of the FDA in 2018, with emphasis on the breakthrough drugs, the milestones in the approved list, and drugs with the highest expected sales in 2024. METHODS: The following scientific search engines were surveyed for the clinical trials of the drugs approved by the FDA in 2018: Pubmed, Springer link, ScienceDirect, Scopus, Wiley online library, Taylor and Francis, and Google Scholar. The total forecast sales were compared based on information from the Cortellis database, EvaluatePharma, and Nature Biobusiness Briefs. RESULTS: The 2018 year was full of good news for the drug market in the USA, with 59 new drug approvals by the FDA, which is the highest number of approvals in the last twenty years. The oncology and the antimicrobial drugs represent almost 50% of the new list, which gives hope to cancer patients and subjects with infectious diseases. In the 2018 FDA list, a number of drugs are expected to exceed 1$ billion dollars of sales by 2024. CONCLUSION: The new drugs approved by the FDA in 2018 have been reviewed. This year showed the highest number of new drug approvals in the last two decades. Among the 59 drugs approved in 2018, 14 drugs are considered breakthroughs, which revive hope for many poorly managed diseases. The list also contains 19 drugs that are first in class and 43 that were given priority reviews.