Liquid-liquid Extraction Research Articles

Exploring the Therapeutical Potential of Asparagopsis armata Biomass: A Novel Approach for Acne Vulgaris Treatment.

Acne vulgaris, a high-prevalence skin condition afflicting people, persists as a significant challenge in the absence of effective treatments and emerging antibiotic resistance. To address this pressing concern, exploration of innovative approaches is of the utmost importance. Asparagopsis armata, an invasive red seaweed renowned for its diverse array of bioactive compounds, emerges as a promising candidate. This study seeks to elucidate the potential utility of A. armata biomass in the treatment of acne vulgaris. Crude extracts were obtained through solid-liquid extraction, and fractions were obtained using liquid-liquid extraction. The analyzed bioactivities included antioxidant, antimicrobial, and anti-inflammatory. Also, chemical characterization was performed to identify free fatty acids and compounds through LC-MS and elements. The present findings unveil compelling attributes, including anti-Cutibacterium acnes activity, cytotoxic and non-cytotoxic effects, antioxidant properties, and its ability to reduce nitric oxide production with consequent anti-inflammatory potential. Additionally, chemical characterization provides insights into its mineral elements, free fatty acids, and diverse compounds. The observed antimicrobial efficacy may be linked to halogenated compounds and fatty acids. Cytoprotection appears to be associated with the presence of glycerolipids and glycosylated metabolites. Furthermore, its antioxidant activity, coupled with anti-inflammatory properties, can be attributed to phenolic compounds, such as flavonoids. This study underscores the potential of A. armata as a natural ingredient in skincare formulations, offering an important contribution to the ongoing battle against acne vulgaris.

Advancing Rare-Earth (4f) and Actinide (5f) Separation through Machine Learning and Automated High-Throughput Experiments.

Identifying improved and sustainable alternatives to "classic" separation techniques is an active research field due to its potential widespread impact in fundamental and applied chemistry. As basic purification methodologies, like liquid-liquid extraction, undergo continuous refinement by chemists and engineers, identifying new conditions that outperform existing techniques can be difficult. A major contributor to this challenging problem is the need to explore a vast experimental space to identify the precise conditions that optimize the separation procedure. The advent of artificial intelligence and the advancement of robotic technologies offer the potential to shift the traditional design paradigm. Toward that end, we applied a combination of Bayesian Optimization and high-throughput robotic experiments on the liquid-liquid extraction of thorium (Th4+) and demonstrated that this approach speeds up discovery and significantly accelerates the optimization process. By using Bayesian Optimization as a guide, our automated instrument carried out a total of 339 distribution ratio measurements, corresponding to 113 unique conditions, identifying the optimal experimental conditions with reduced experimental efforts by an estimated 74% compared to a traditional full screening approach. This time and cost saving is particularly significant for radioactive materials, as it not only is more economical and sustainable but also minimizes human exposure to radioactivity.

Determination of nobiletin and tangeretin in rat plasma by ultra-performance liquid chromatography-tandem mass spectrometry and study of their pharmacokinetics

AbstractAn ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of nobiletin and tangeretin in rat plasma, and the plasma was processed by a simple liquid-liquid extraction method with ethyl acetate. The chromatographic column was UPLC HSS T3 (50 × 2.1 mm, 1.7 μm), the mobile phase was acetonitrile-water (containing 0.1% formic acid). Multiple reaction monitoring mode (MRM) was used for quantitative analysis, nobiletin m/z 403.29 → 373.14 (cone voltage 22v, collision voltage 28v), tangeretin m/z 373.28 → 343.17 (cone voltage 20v, collision voltage 28V), tangeretin m/z 373.28 → 343.17 (cone voltage 20V, collision voltage 28V) and internal standard vitexin m/z 433.14 → 313.03 (cone voltage 32v, collision voltage 26v). The pharmacokinetics of nobiletin and tangeretin were evaluated in rats. The established UPLC-MS/MS method in the range of 2–2,000 ng mL−1 was successfully applied to the pharmacokinetics, and the calculated bioavailability of nobiletin and tangeretin was 63.9 and 46.1%, respectively.

A Simple HPLC-DAD Method for the Therapeutic Monitoring of Clozapine and Related Metabolites in Human Plasma and Urine Samples.

Clozapine and its metabolites require close therapeutic monitoring (TDM) in patients due to poor correlation between the administrated doses and resulting plasma concentrations, the narrow therapeutic interval, high inter-individual variability, and the risk of serious side effects once toxic levels are exceeded. The aim of the study was to develop a simple (relatively cheap) LC-UV method for the quantification of clozapine and its metabolites in plasma and urine samples. For sample preparation, liquid-liquid extraction (LLE) in n-octanol was more efficient and less limiting in injection volumes compared to the in-situ formation of SUPRAS. When analyzing urine, an alkalinization step before extraction was required. The proposed method produced linear concentration responses with/without internal standard (IS) for the target analytes, with LLOQs within the targeted range of 50 ppb and %RSD within the acceptable 15% range. Furthermore, sample stability studies proved that pre-extracted samples were stable for the short term at room temperature and long-term when frozen.

Tetrafunctionalized Azocalix[4]resorcinarene Dye: A Chromogenic Supramolecule Used for the Selective Liquid-Liquid Extraction and Spectrophotometric Determination of Cu(II)

Background: The detection and extraction of trace metal ions, particularly copper(II), are critical for environmental monitoring and industrial processes. Calixresorcinarene, with its unique cavity structure, offers excellent platforms for designing selective chemosensors and extractants. Functionalization of calixresorcinarene with azo groups can enhance their chromogenic properties, enabling both extraction and detection in a single step. Objective: This study aimed to evaluate its (Azocalix[4]resorcinaren) efficacy as a selective chemosensor for the liquid-liquid extraction and spectrophotometric determination of Cu(II) ions. Methods: Application in Extraction and Detection: The ability of the dye to selectively extract Cu(II) ions from aqueous solutions was investigated via liquid-liquid extraction experiments. The dye-Cu(II) complex formation was monitored by UV-Vis spectrophotometry, with systematic optimization of experimental conditions, including pH, solvent system, and extraction duration. Results: The synthesized azocalix[4]resorcinarene dye exhibited a pronounced selectivity towards Cu(II) ions, forming a stable, colored complex. The complexation induced a distinct bathochromic shift in the absorption spectrum, allowing for precise spectrophotometric detection. Optimal extraction was achieved at a specific pH and solvent combination, with the method demonstrating a low detection limit and high sensitivity. The dye showed minimal interference from other metal ions, confirming its selectivity for Cu(II). Conclusion: The tetrafunctionalized azocalix[4]resorcinarene dye is a highly effective chromogenic agent for the selective extraction and detection of Cu(II) ions. Its robust performance in both extraction efficiency and spectrophotometric detection underscores its potential utility in environmental analysis and industrial applications where trace metal detection is crucial.

Measurement Uncertainty and Validation for Quantification of Marijuana Metabolite: (−)-11-nor-9-Carboxy-Δ9-THC in Human Urine by GC-MS/MS

Background: Since the International Olympic Committee (IOC) was established, sports doping control analyses have revealed a high rate of positive cases for cannabinoids. Cannabinoids were banned in all sports where they were used in competition as per the Prohibited List published annually. Further, it was also included in the threshold drug category. Consequently, developing a reliable method for urine Cannabinoids metabolite quantification plays a pivotal role in sports dope testing. Objective: This work aimed to develop and validate a reliable, cost-effective, robust gas chromatography-tandem mass spectrometry method for detecting (−)-11-nor-9-Carboxy-Δ9- THC component in human urine samples, in compliance with ICH and WADA guidelines. Method: The sample preparation was done by enzymatic hydrolysis for deconjugation, further proceeded with solid phase extraction (SPE), liquid-liquid extraction (LLE), and using an XAD2 column, and N-methyl trimethylsilyl trifluoroacetamide (MSTFA) for derivatization. Results: The linearity was obtained in a range of 50–300 ng/mL, and the correlation coefficient was found to be higher than 0.99. Throughout the entire validation study, the difference in Retention Time (RT) for the analyte, including the Internal Standard (IS), was shown to be less than 1.0%. The quantification limit (LOQ) was calculated at a level of 50 ng/mL in human urine samples for the 3 most abundant ion transitions. The detection limit (LOD) was established at 4 ng/mL. Conclusion: The accuracy, precision, linearity, recovery, quantification limit, and selectivity by GC-MS/MS technique were found acceptable and well satisfactory while following the ICH guidelines. The developed method has been proven to be fit for purpose in accordance with the enforced Guidelines of WADA.

Efficient Online TurboFlow Method for Simultaneous Determination of 60 Emerging Per- and Polyfluoroalkyl Substances in Milk.

Emerging perfluoroalkyl and polyfluoroalkyl substances (PFASs) have received much attention in recent years. Milk has usually low concentrations of PFASs, but it remains an important PFAS exposure route due to its high consumption. In this study, a method for simultaneous determination of 60 PFASs in milk was developed by online TurboFlow liquid chromatography-tandem mass spectrometry. A pH-dependent cold-induced liquid-liquid extraction was developed for precleanup and enrichment. Method quantification limits ranged from 0.003 to 0.500 ng/mL. For PFASs without corresponding isotope-labeled internal standards, Tanimoto coefficient and logP were introduced for the selection of internal standards. The matrix spiked recoveries ranged from 47 to 190%. The method was applied for PFAS analysis in 35 milk samples. PFBS, perfluorohexanesulfonic acid, perfluorooctanesulfonic acid, PFNS, PFPeA, perfluorooctanoic acid, PFNA, and 6:2 FTS were detected. The developed online TurboFlow method was simple, reliable, efficient, and applicable for trace analysis of PFASs in milk.

Styrene divinyl benzene beads (SM-2) functionalized with triisobutylphosphine sulfide for selective uptake of palladium(II) from nitric acid medium

Resins impregnated with organic extractants regarded as effective adsorbent materials due to their ability for selective sorption. These resins consist of a polymeric material that is infused with accessible organic extractants. Furthermore, these resins merge the unique properties and the distinctive characteristics of both liquid-liquid extraction and solid-liquid sorption processes. In this work, the impregnation of Styrene divinyl benzene beads (SM-2 beads) with triisobutylphosphine sulfide (TIBPS = CYANEX 471X) was prepared. A SM-2 bead functionalized with CYANEX 471X (SM-2-TIBPS beads) was characterized using scanning electron microscope (SEM) and Fourier-transform infrared spectroscopy (FT-IR) techniques and investigated for recovery and separation of palladium ions from a 3 M nitric acid solution. Various parameters were studied, as shaking time effect, nitric acid concentration, SM-2-TIBPS beads weight, Pd(II) concentration and temperature. The Pd(II)/SM-2-TIBPS sorption system has an endothermic nature and was fitted with a Langmuir isotherm model with a 0.9860 regression factor. The kinetics modeling was fitted with PSO and IPD models with regression factors of 0.9889 and 0.9959, respectively. The maximum monolayer sorption capacity of SM-2-TIBPS was found to be 17.47 ± 0.9 mg/g. The sorption of Pd(II) from different media at 3 M takes the following sequence: HNO3 > HCl > H2SO4. Desorption of about 76.38 ± 2.4% was achieved with (1 M + 1 M) of thiourea + HCl after one desorption stage. Effect of other interfering ions, as Pt(II), Pb(II), Eu(III), Cu(II), Mo(VI), Co(III), Zr(IV), Fe(III), Cd(II), and Ce(III), indicates high separation factors between Pd(II) and other investigated metal ions, which ranged from 9.4 to 35.

Rapid Liquid Chromatography-Tandem Mass Spectrometry Method for Determination of Total and Free Testosterone in Human Serum and Its Application to Monitoring Biomarker Response of Elite Athletes.

Total testosterone (TT) and free testosterone (FT) are important biochemical markers for anabolism of the human body, and can also serve as early screening indicators for overtraining syndrome (OTS). Presently, there is no fast and reliable serum TT and FT determination method in the field of sport science that can meet the requirements of sports research. Thus, a rapid and accurate determination method for serum TT and FT to fill the gap is needed urgently in sports training. Herein, a simple and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of TT and FT in serum was developed and fully validated, followed by the application of professional athletes in training monitoring. Efficient pretreatments based on only one-step liquid-liquid extraction (LLE) for TT and one-step LLE after a 20 min ultrafiltration for FT were adopted in this study, and the isotope internal standard of testosterone-13C3 was used to ensure the reliability of the whole procedure. A linear range of four orders of magnitude with 0.02-100 ng/mL can meet the concentration range requirement between a higher limit for male TT and a lower limit for female FT. The accuracy, precision, stability, and matrix effect were all within the limits of the guidelines. The serum TT and FT levels of 200 professional athletes (98 male athletes and 102 female athletes) were investigated by this method. Serum TT, FT, and FT/TT levels of professional athletes were significantly higher than the general population, and serum TT levels were significantly higher by LC-MS/MS than by a chemiluminescence immunoassay. In conclusion, the LC-MS/MS method for TT and FT measurement developed in this study is time-saving and easy to operate, which can be used as a reliable method for the determination of serum TT and FT in sports training, offering valuable information for monitoring anabolism of athletes and screening OTS in the early stage.

Critical analysis of analytical techniques developed for statins in biological fluids, environmental and fermentation samples.

Statins are the most prescribed drug for regulating the high cholesterol level in the blood, which can lead to severe complications, such as cardiovascular diseases and other health complications. A wide range of analytical techniques have been employed for the quantification of statins from various origins, including fermentation derived (lovastatin, pravastatin, and compactin), semi-synthetic (simvastatin), and synthetic (atorvastatin, rosuvastatin, and fluvastatin) routes. The presence of more than one structural form and structural analogue generated in the biosynthesis pathway, as well as reaction intermediates and macromolecules in the clinical sample, complicates the quantification of statins. Furthermore, significant concentrations of statins in environmental samples pose serious health and ecology hazards, and estimating statins in those diluted samples is extremely difficult. On the other hand, the: cost, accurate estimation of the desired one from other structural forms, sample complexity, time, limits of detection and quantification, were major criteria distinguishing the usability of each technique. As a result, the current manuscript focuses on analytical techniques such as molecular spectroscopy (normal and derivatives UV-Visible spectrophotometer), chromatography (TLC, HP-TLC, HPLC, GC, swing column, micellar, and supercritical fluid), mass spectroscopy (HPLC-MS/MS and GC-MS/MS), sequential flow injection, capillary electrophoresis, and cyclic voltammetry, as well as their: optimal operating conditions, limits of detection and quantification, advancements, and limitations. Furthermore, various online and offline sample preparations (precipitation, solid phase extraction, liquid-liquid extraction, and micellar extraction) have been highlighted as an essential pretreatment technique to avoid the interference caused by structural analogues and other macromolecules. The greener and more sustainable concepts used in analytical approaches for the quantification statins are also highlighted with current advancements.

Optimizing Membrane Performance using Various Filler Materials in Membrane Fabrication for Enhancing Gas Separation Efficiency: A Review

The membrane technology has been receiving significant interest in both research and industrial applications, particularly in the separation of CO2/CH4. These methods, as published, aim to overcome the limitations of pure polymeric membranes and offer an alternative approach in separation techniques where membrane technology can overcome the constraints of conventional methods such as Solid Phase Extraction (SPE) and Liquid-Liquid Extraction (LLE). Fabricating membranes using fillers as adsorbents can enhance membrane separation performance due to their porous nature. Hence, the selection of suitable fillers is crucial to maximize membrane efficiency in separating analytes. This paper will review 3 types of fillers-metal-organic frameworks, carbonaceous nanomaterials and mesoporous molecular sieves-from various research papers published in recent years. HIGHLIGHTS Additives introduced to polymeric membrane to increase the membrane performances in terms of selectivity and permeability. Short review of materials used for fabrication of mixed matrix membrane. Modification of selected additives used to study its effects on membrane performances. Recent advancement of hybrid additives materials, combining MOF and carbonaceous materials. GRAPHICAL ABSTRACT

Development and Validation of an Improved HPLC-MS/MS Method for Quantifying Total and Unbound Lenalidomide in Human Plasma.

This study aimed to develop a fully validated HPLC-MS/MS method for quantifying total and unbound lenalidomide concentrations in human plasma. Unbound concentrations were measured using plasma ultrafiltrate prepared with Amicon® Centrifugal Filters. Lenalidomide and lenalidomide-d5 (internal standard) were extracted from 50 μL of human plasma using liquid-liquid extraction. Chromatography was conducted with a Halo® C18 column using 0.1% formic acid and methanol (20:80, v/v) as the mobile phase. The mass spectrometer was operated in a positive ion mode with an electrospray ionization interface and multiple reaction monitoring modes. Calibration curves were linear over the range of 5 to 1000 ng/mL (r2 > 0.996) for both the total and unbound lenalidomide. For total lenalidomide concentrations, between-run precision (coefficients of variation) and accuracy were 1.70-7.65% and 94.45-101.10%, respectively. For unbound concentrations, inter-day precision and accuracy were 1.98-10.55% and 93.95-98.48%, respectively. We developed a highly reproducible, sensitive, and efficient bioanalytical method using a smaller volume of plasma sample (50 μL) with a relatively short run time (2.5 min). The proposed analytical method was successfully applied to measure total and unbound lenalidomide concentrations at various time points in multiple myeloma patients with renal impairment.

Evaluating the detection of barbiturates in dried blood spots: A comparative analysis using gas chromatography-mass spectrometry, gas chromatography-tandem mass spectrometry, and liquid chromatography-tandem mass spectrometry with different extraction methods

Rapid and accurate characterization and quantitation of blood barbiturates and their combination drugs are very important for the clinical treatment of acute barbiturate poisoning. A comparison of dried blood spot (DBS) and traditional liquid-liquid extraction (LLE) in the pre-treatment stage, as well as a comparison of gas chromatography-mass spectrometry (GC–MS), gas chromatography-tandem mass spectrometry (GC–MS/MS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) as instrumental analysis methods, revealed differences in the analysis results of barbiturates and their combination drugs under different conditions. Based on these findings, we introduce a DBS-GC–MS/MS method. The developed and validated method showed good selectivity, sensitivity (LOD: 0.1 μg mL−1, LOQ: 0.2 μg mL−1), linearity (R2>0.9992), trueness (<15 %, except for carbamazepine, at 29.4 %), and precision (<15 %). Recovery was also good for most target compounds, but significant matrix effects were evident. Compared with the LLE method, the DBS method has the benefits of easy sample collection, storage, and transport, as well as simple pre-treatment and reduced reagent and energy consumption. Compared to LC-MS/MS, GC–MS/MS requires no switching between positive and negative ion modes and uses the MRM detection mode, meaning that more information about the sample compounds can be obtained in less analysis time. Using actual sample analysis, we have demonstrated the advantages of the DBS-GC–MS/MS method for the qualitative and quantitative analysis of barbiturates and poisoning events due to combinations of these drugs. Comparison of the three instruments and the two treatment methods revealed their analysis characteristics. From the perspective of practical application, the broad practical value and advantages of DBS should be embraced in more applications, and future analytical laboratory development should continue to recognize GC–MS/MS as a useful supplement to LC-MS/MS.

Introducing Phosphate Ester into DAPhen by Propyl Enhanced the Selectivity for UO22+ over Th4.

A new type of phenanthroline carboxamide(DAPhen)-phosphate ester ligand (L1/L2) was synthesized for the selective separation of U(VI) over Th(IV). Liquid-liquid extraction experiments showed that the introduction of phosphate ester could increase the extraction ability of ligands for U(VI), especially L2, which showed high selectivity for the separation of U(VI) over Th(IV). The slope analysis indicated that L1 could form 1:1 and 1:2 complexes with U(VI) and 1:1 complexes with Th(IV). NMR titration revealed that the DAPhen unit of ligands combined with one U(VI) to form 1:1 complexes, and then the phosphate ester unit of the 1:1 complexes further combined with another U(VI) to form 1:2 complexes. Ligands provide only the DAPhen unit to Th(IV) to form 1:1 complexes. The crystal structures found 1:2 complexes of L1 and U(VI), 1:1 complexes of L2 and U(VI), and 1:1 complexes of L1 and Th(IV). The larger stability constant (log β) of the 1:1 complexes of L2 with U(VI) than that of the 1:1 complexes of L1 with U(VI) showed that the binding ability of U(VI) with the DAPhen unit of L2 is stronger than that of U(VI) with the DAPhen unit of L1. This study provides new ideas for designing extractants with excellent properties.

Application of salt-assisted liquid extraction in bioanalytical methods

This review provides a comprehensive analysis of bioanalytical methods employed for the quantification of drug molecules in various biological matrices, including human plasma, urine, breast milk, and mouse plasma. The study not only examines traditional sample preparation techniques such as protein precipitation (PP), liquid-liquid extraction (LLE), and solid-phase extraction (SPE), but also delves into the relatively new and innovative salting-assisted liquid-liquid extraction (SALLE). It offers a thorough comparison of analytical methods utilizing SALLE, focusing on key parameters such as analysis time, calibration range, and the type and quantity of salts and organic solvents used. This review aims to serve as an essential resource for researchers and practitioners in selecting the most suitable bioanalytical methods for pharmacokinetic studies and drug monitoring, ultimately enhancing data quality and analytical efficiency in both clinical and research settings.

Development of a Versatile High-through-put Oligonucleotide LC-MS Method to Accelerate Drug Discovery.

Liquid chromatography-mass spectrometry (LC-MS) is an effective tool for high-throughput quantification of oligonucleotides that is crucial for understanding their biological roles and developing diagnostic tests. This paper presents a high-throughput LC-MS/MS method that may be versatilely applied for a wide range of oligonucleotides, making it a valuable tool for rapid screening and discovery. The method is demonstrated using an in-house synthesized MALAT-1 Antisense oligonucleotide (ASO) as a test case. Biological samples were purified using a reversed liquid-liquid extraction process automated by a liquid handling workstation and analyzed with ion-pairing LC-MS/MS. The assay was evaluated for sensitivity (LLOQ = 2nM), specificity, precision, accuracy, recovery, matrix effect, and stability in rat cerebrospinal fluid (CSF) and plasma. Besides some existing considerations such as column selection, ion-pairing reagent, and sample purification, our work focused on the following four subtopics: 1) selecting the appropriate Multiple Reaction Monitoring (MRM) transition to maximize sensitivity for trace-level ASO in biological samples; 2) utilizing a generic risk-free internal standard (tenofovir) to avoid crosstalk interference from the oligo internal standard commonly utilized in the LC-MS assay; 3) automating the sample preparation process to increase precision and throughput; and 4) comparing liquid-liquid extraction (LLE) and solid-phase extraction (SPE) as sample purification methods in oligo method development. The study quantified the concentration of MALAT-1 ASO in rat CSF and plasma after intrathecal injection and used the difference between the two matrices to evaluate the injection technique. The results provide a solid foundation for further internal oligonucleotide discovery and development.

Development of a UHPLC-MS/MS Method for the Determination of Moxidectin in Rat Plasma and Its Application in Pharmacokinetics.

The aim of the present study was to establish a simple and reliable ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method and apply it for the determination of pharmacokinetics of moxidectin-loaded microspheres (MOX-MS) in rats. Plasma samples were processed using a simplified liquid-liquid extraction method and were separated using an Agilent Zorbax Eclipse Plus C18 column (50 mm × 2.1 mm, 1.8 μm) with a mobile phase consisting of a 10 mM ammonium formate solution with 0.1% formic acid (A) and acetonitrile (B) at a flow rate of 0.4 mL/min for 5 min. Avermectin B1a was used as an internal standard (IS). The sample was injected at a volume of 10 μL with a column temperature of 35 °C and detected in a positive ion mode. A good linear response across the concentration range of 1.00-200 ng/mL (r2 > 0.99) and a lower limit of quantification (LLOQ) of 1.00 ng/mL were achieved. The extraction recovery of moxidectin exceeded 94.1%, the matrix effect was between 91.2% and 96.2%, the accuracy ranged from 100.1 to 103.6%, and the relative standard deviation (RSD) did not exceed 15% for the intra- and inter-day accuracy and precision. The pharmacokinetic results showed that MOX-MS significantly decreased Cmax, prolonged T1/2, and improved bioavailability. The developed method significantly reduced the assay volume, shortened detection time, simplified sample processing methods and saved assay costs, which may contribute to the development of the new antiparasitic drug.

Revealing the backbone structures of land-based fulvic acids derived from river and soil through n-butylsilane reduction.

While ultra-high-resolution mass spectrometry has enabled the identification of the molecular composition of dissolved organic matter (DOM), elucidating its molecular structure remains a challenging endeavor. Here, two fulvic acids (FAs), one from river and the other from forest soil, were subjected to reduction using an optimized n-butylsilane (n-BS) reduction method. The reduction products were purified through a combination of liquid-liquid extraction and silica gel column chromatography, resulting in the separation into saturates, aromatics, and polar products. The polar products were analyzed by high-resolution mass spectrometry (HRMS), and the saturates and aromatics were analyzed using gas chromatography-mass spectrometry (GC-MS). HRMS results showed that the number of oxygen atoms and double-bond equivalent (DBE) values of FA decreased after reduction. GC-MS results revealed that a total of 270 hydrocarbon monomers were identified from the reduction products of a single sample, with the highest carbon number of cycloalkanes reaching C33. For the first time, steranes and hopanes were detected in the reduction products, potentially serving as evidence for the existence of carboxyl-rich alicyclic molecule (CRAM) precursors. Additionally, a significant number of polycyclic aromatic hydrocarbons were identified, and the potential sources of various compounds were preliminarily inferred based on their isomers. This study extends the knowledge of the possible backbone structure of the DOM and provides a new potential tool for investigating the origin and transformation mechanisms of DOM.

Innovative Techniques for Pharmaceutical Waste Management: Enhancing Drug Recovery and Environmental Sustainability

The pharmaceutical sector is a major component of current healthcare, manufacturing and distributing drugs, biological substances, and medical equipment. Despite its advantages, the sector creates enormous waste, including materials for packaging, production by-products, expired or unused drugs, and other residues, creating health and environmental issues. Appropriate pharmaceutical waste handling and medication recovery strategies are vital for limiting these problems. This article aims to investigate and evaluate multiple techniques for recovering pharmaceuticals from pharmaceutical waste, highlighting the significance of sustainable waste management in the pharmaceutical sector. The paper emphasizes the need to use modern methods such as liquid-liquid extraction, membrane crystallization, solid-liquid extraction, and adsorption to recover drugs from pharmaceutical waste. Liquid-liquid extraction exhibits excellent adaptability and efficiency for varied Active Pharmaceutical Ingredients (APIs), whereas membrane crystallization provides low-energy solutions for thermally sensitive compounds. Solid-liquid extraction is useful for recovering APIs from solid dosage forms, while adsorption approaches exploit substances like activated carbon for organic component recovery. Each process has particular benefits and disadvantages, with the selection of methodology based on waste properties and recovery objectives. It emphasizes the promise of these technologies for high extraction yields, purity, and environmental sustainability, supporting effective pharmaceutical waste management procedures. Additionally, difficulties such as cost-effectiveness, scalability, and regulatory compliance are addressed, pointing to opportunities for future research and development to improve the efficacy of drug recovery procedures. In conclusion, using advanced techniques to recover pharmaceuticals from pharmaceutical waste offers a viable way to implement sustainable waste recovery procedures and lessen the pharmaceutical industry's negative environmental effects.

Quantitation of the DNA-dependent protein kinase inhibitor peposertib (M3814) and metabolite in human plasma by LC-MS/MS.

The DNA-dependent protein kinase (DNA-PK) is an abundant nuclear protein that mediates DNA double-strand break repair by nonhomologous end joining (NHEJ). As such, DNA-PK is critical for V(D)J recombination in lymphocytes and for survival in cells exposed to ionizing radiation and clastogens. Peposertib (M3814) is a small molecule DNA-PK inhibitor currently in preclinical and clinical development for cancer treatment. We have developed a high-performance liquid chromatography-mass spectrometry method for quantitating peposertib and its metabolite in 0.1 mL human plasma. After MTBE liquid-liquid extraction, chromatographic separation was achieved with a Phenomenex Synergi polar reverse phase (4μm, 2× 50 mm) column and a gradient of 0.1% formic acid in acetonitrile and water over an 8min run time. Mass spectrometric detection was performed on an ABI SCIEX 4000 with electrospray, positive-mode ionization. The assay was linear from 10 to 3000 ng/mL for peposertib and 1-300 ng/mL for the metabolite and proved to be both accurate (97.3%-103.7%) and precise (<8.9%CV) fulfilling criteria from the Food and Drug Administration (FDA) guidance on bioanalytical method validation. This liquid chromatography-tandem mass spectroscopy (LC-MS/MS) assay will support several ongoing clinical studies by defining peposertib pharmacokinetics.