Solvent Extraction System Research Articles

Quaternary solvent system for highly efficient separation and purification of glabridin by fractional extraction

• A quaternary solvent extraction system was explored to separate and purify glabridin. • The extraction system is green and simple without reactive extractant. • A mathematical model was established to simulate and optimize extraction process. • Residual rate is introduced to describe product purity and impurity content. • Glabridin with high purity and yield has been obtained continuously. A quaternary solvent extraction system was used to separate and purify glabridin from a crude extract of Glycyrrhiza glabra L. The influence of solvents and their ratios on the distribution of glabridin was examined to develop an efficient quaternary solvent extraction system. For the optimal solvent extraction system, the organic phase consisted of 22.64% butyl acetate, 73.80% hexane, 0.24% water and 3.30% ethanol (W/W), and the water phase consisted of 1.79% butyl acetate, 0.57% hexane, 56.09% water and 41.55% ethanol (W/W). To determine the ideal parameters for separation, a mathematical model was used to simulate and optimize the multi-stage processes. The yield and residual rate were used as the purity reference to simulate the separation of glabridin. Under the optimal conditions, two series of ten-stage and twenty-stage centrifugal extractors were successfully used to separate glabridin. The yield and purity of glabridin were 85% and 94%, respectively, after twenty-stage separation.

Selective extraction of heavy metals (Fe, Co, Ni) from their aqueous mixtures by Task-Specific salicylate functionalized imidazolium based ionic liquid

Iron (Fe), cobalt (Co) and nickel (Ni) together are known as the iron triad exhibiting similar chemical and physical affinities in the periodic table. We have developed a green, efficient, highly selective, environmentally benign, water-IL biphasic solvent extraction system for the selective extraction of iron triad elements from their aqueous mixtures at room temperature using a new salicylate functionalized imidazolium based task specific ionic liquid (TSIL) i.e. 1,3-dioctylimidazolium 2-hydroxybenzoate [DOIM][OHB]. Co2+ was extracted within 5 min as a blue complex while the residual mixture was allowed to stand overnight. In the meantime, Fe2+ was oxidized to Fe3+ without using any additional oxidants and was extracted as a red coloured complex. Ni2+ was not observed visibly, however atomic absorption spectroscopy (AAS) indicated the presence of less than 1% Ni2+. The extraction of heavy metal ions follows neutral extraction mechanism elucidated through UV visible spectroscopy.

Modelling of lithium extraction with TBP/P507–FeCl3 system from salt-lake brine

• A thermodynamic model was developed for Li extraction by TBP/P507/FeCl 3 system. • The model parameters were optimized by fitting the calculated to experimental data. • Extraction mechanism was clarified by modelling species distribution in organic. Recovery of lithium from Mg-rich salt-lake brines by solvent extraction has been widely studied for high Li + /Mg 2+ selectivity and Li + extraction efficiency. In a previous study, a ternary synergistic solvent extraction system consisting of tributyl phosphate (TBP), 2-ethylhexyl phosphonic acid mono-2-ethylhexyl ester (P507, denoted as HL) and FeCl 3 was developed, in which high Li + selectivity and efficient Li + stripping simply with water were realized. In this study, to further elucidate the extraction mechanism of the TBP/P507/FeCl 3 system and minimize the efforts on the process optimization for Li extraction from Mg-rich salt-lake brines with different component concentrations from different sources, a thermodynamic empirical model based on mass balances and equilibrium equations has been developed. The model parameters were optimized by fitting the calculated data to experimental results. By calculating the distribution of species in the organic phase with the model, it was found that Li + primarily existed in the form of [Li(TBP) 2 ][FeCl 4 ], followed by [Li(TBP)][FeCl 4 ]. When Li + was stripped with water, Fe 3+ mainly existed in the form of FeCl 2 L·HL·2TBP in the organic phase at low O/A ratios but converted to [H(TBP) 2 ][FeCl 4 ] at high O/A ratios. This thermodynamic model provides a guide for the design of practical process flow.

Synthesis of N-(2-ethylhexyl)-pyridine-4-carboxamide and its synergistic behaviors with dinonylnaphthalene sulfonic acid for the selective extraction of nickel and cobalt

The hydrometallurgical process for the recovery of nickel and cobalt requires a complex and expensive impurity removal process. Solvent extraction is widely used in industry for the separation, purification, and concentration of metals. However, current commercial extractants encounter some difficulties when cobalt and nickel are extracted from solutions containing a large amount of impurities such as manganese and calcium. There is an urgent need to develop new reagents for the selective extraction of Ni and Co. In this study, N-(2-ethylhexyl)-pyridine-4-carboxamide (NEHPCA) was synthesized, and the metal extraction capacity of its synergistic solvent extraction (SSX) system with dinonylnaphthalene sulfonic acid (DNNSA) and tributyl phosphate (TBP) modifier was examined. The experimental results show that the selectivity of the new SSX system has the order Cu > Ni > Co > Zn > Mn > Ca > Al ≈ Cr (III) ≈ Mg ≈ Fe (III), with excellent selectivity for nickel and cobalt. Using an organic phase composed of 0.7 M NEHPCA, 0.35 M DNNSA, and 0.2 M TBP under 1:1O/A operation, after three-stage theoretical extraction, more than 99% of nickel and cobalt can be recovered from a synthetic leaching solution of nickel laterite ore. Mechanistic studies showed that NEHPCA and water molecules participate in the internal coordination of metals, and DNNSA provided coordination anions to achieve charge balance, forming the Ni complex in this SSX system which existed most likely in the form of [Ni(NEHPCA)2(H2O)4](DNNS)2 in the organic phase.

The study on extraction behavior of [N1888][P507] and TRPO for heavy rare earths

Ionic liquids were extensively used in many extraction and separation processes for metal ions because of excellent dissolving and selecting ability. The COSMO-RS method was applied for selecting suitable ionic liquid from 80 kinds of ionic liquids. Hydrophilicity, solvent solubility, distribution ratio were considered as important factors for selecting suitable ionic liquids. [N1888][P507] was suitable ionic liquid for extracting and separating heavy rare earths. A solvent extraction system containing ionic liquid [N1888][P507] and molecular extractant TRPO to separate heavy rare earths was studied. The results showed that the mixture of the [N1888][P507] and TRPO contributed to high extractabilities and selectivities of heavy rare earths. The abilities to form third phase and product emulsification phenomenon decreased with the concentration ratio of TRPO and [N1888][P507] increasing. The extraction mechanism of HREEs was deduced as ion association. The quantitative stripping of HREEs from loaded organic phase could be achieved with deionized water and low concentration of hydrochloric acid. The article showed that the mixture of [N1888][P507] and TRPO might be an effective and environmentally friendly extractant for extraction and separation of heavy rare earths.

Potential Sources of Natural Antioxidants and Antimicrobials: Comparative Analysis of Turmeric (Curcuma longa) Extracts from Different Solvent Extraction Systems

Jolly Oder Akullo, Beatrice N Kiage-Mokua, Dorothy Nakimbugwe, Jeremiah Ng’ang’a and John Kinyuru Phytochemical content and activity of organic and aqueous extracts of turmeric (Curcuma longa) was studied to determine their potential for use as natural antioxidants and antimicrobials for therapeutic and food applications.

Speculation of feasible interaction between tri-n-octyl amine and Di-2-ethylhexylphosphoric acid from volumetric measurements

Solvent extraction serves as one of the most proven hydrometallurgical techniques for recycling and recovery of various metal values This extraction practice is based on the shuttling of the solute molecules between two non-miscible liquid phases. The affinity of the solute is motivated by the nature of the extracting agent to initiate the transference of the solute from the feed solution to the organic phase. Therefore, choice of suitable extractants plays a crucial role in solvent extraction systems. Binary extractant systems have been more effective with improved separation ability and have drawn more attention in the field of solvent extraction. The investigation of interaction between the extracting agent and diluent, two main components of the organic phase, has immense impact on the extraction efficiency. Scrutiny of physicochemical properties like molar volume, partial molar volume apparent molar volume and excess molar volume, is essential in order to obtain more insight about the synergistic extractant mixtures. The present work reports the volumetric properties of binary mixtures of a basic extractant, tri-n-octyl amine (TOA) and an acidic extractant, di-2-ethylhexylphosphoric acid (D2EHPA) at T = 298 K-318 K to predict the possible interaction existing between these two at different mole fractions. By rising the mole fraction of TOA in the mixture, the density of the binary mixture gradually decreases. Enhancement in temperature resulted an increase in molar volume of the binary mixture.

Analysis of the kinetics ions Ho(III), Pr(III), Gd(III) transport at the liquid-liquid interface in the presence of a magnetic field gradient

In the present work, the kinetics of transport of selected rare earth ions at the liquid-liquid interface in the presence of a magnetic field gradient was investigated. A uniform magnetic field was applied to the classic liquid-liquid solvent extraction system. The influence of temperature, initial concentration of selected ions and magnetic field gradient on the extraction rate was determined. It was shown that the uniform magnetic field could affect the kinetics of the extraction of rare earth ions in the liquid-liquid system. The observed differences constitute a promising prospect worthy of further research. Figs 6, Refs 10.

Extraction Mechanism of Germanium in Sulfate Solutions Using a Tertiary Amine (N235)-Based Solvent Extraction System

Extraction Mechanism of Germanium in Sulfate Solutions Using a Tertiary Amine (N235)-Based Solvent Extraction System

Effect of alkyl chain configuration of tertiary amines on uranium extraction and phase stability – Part I: Evaluation of phase stability, extraction, and aggregation properties

Amine-based extraction processes are broadly exploited for the selective extraction of uranium from sulfuric leaching liquors. The molecular forces (that is, the enthalpy associated with the multi-scale structuration of tertiary amines) are balanced by entropic effects that have not yet been identified. This first part in a series of reports describes the effects of the alkyl chain configuration on the phase stability and aggregation properties of tertiary amines. It is demonstrated that tertiary amines with longer or slightly branched alkyl chains provide better phase stability and enable constant extraction of uranium. In comparison, more branching of the alkyl chains hinders the formation of a highly curved interfacial layer, thus preventing efficient extraction. Combined small-angle scattering determination of the nanostructures in the organic phase and oil–water surface tension measurements revealed that the alkyl chains effects on the efficiency of the extraction process and phase stability are associated with reverse aggregates with smaller polar core volumes and less co-extracted water, suggesting that packing of the alkyl chains has a direct impact on the extraction efficiency of the solvent extraction system.

Numerical simulation to estimate the droplet size in aerosol solvent extraction system

The aerosol solvent extraction system (ASES) is one of the emerging processes for the production of fine particles of pharmaceutical compounds. This process involves atomization of the solution (pharmaceutical compound + organic solvent) in an antisolvent environment. The atomized droplet comes in contact with the antisolvent, the latter diffuses into the droplet and the solvent evaporates from the droplet surface. This work presents a mathematical model to calculate the dynamic size of a droplet moving in a precipitator used in the supercritical antisolvent process. The system considered for this work is carbon dioxide (CO2)-dimethyl sulfoxide (DMSO). Two Film Theory of mass transfer is used to estimate the mass transfer to and from the droplet. This two-way mass transfer process results in extremely high, very rapid and uniform supersaturation, which leads to the formation of very small size particles with narrow size distribution. The simultaneous diffusion of CO2 and the evaporation of solvent from the droplet cause swelling of the droplet which may be followed by shrinking. The effects of process parameters such as nozzle diameter, flow rate on droplet size are also studied in this work.

Effect of Solvent on Antioxidant Activity of Zanthoxylum oxyphyllum Edgew and its DFT Study

Background: Free radicals can easily damage DNA, proteins and lipids within the tissue. Anti-oxidants from natural sources can diminish the actions of free radicals. The current study deals with the chemical composition and antioxidant activity of the leaves of Zanthoxylum oxyphyllum Edgew. Methods: The antioxidant activities for DPPH, FRAP, ABTS radicals, phosphomolybdate assay, reducing power, and chelating power assay were evaluated of ethanol (ET), methanol (ME), chloroform (CH), ethyl acetate (EA), and petroleum ether (PE) extracts of the leaves. The Density Functional Theory (DFT) study was carried out on major identified phytochemicals to evaluate bioactive molecules responsible for the antioxidant activity. Results: It was observed that the ME extract showed the most potent scavenging activity in DPPH, FRAP, ABTS radicals, phosphomolybdate assay, reducing power, and chelating power assay. The phenolic acids and flavonoids like quercetin, gallic acid, sinapic acid, etc. were identified. The DFT study was done for major phytochemicals of ME extract to evaluate the most responsible bioactive molecule for antioxidant activity. The Gallic acid exhibited the lowest bond dissociation energy (BDE) of 314.9 kcal/mol in gas, 309.2 kcal/mol in methanol, respectively, along with the highest value of radical stabilization energy (RSE), 29.5 kcal/mol. Conclusion: Gallic acid was found to be the most responsible antioxidant among the other compounds, and ME the best solvent system for extraction, followed by CH.

Application of solvent pH under pressurized conditions using accelerated solvent extraction and green solvents to extract phytonutrients from wild berries

Berry fruits are known as “superfoods” due to health benefits associated with the high content of bioactive compounds or phytonutrients. Organic extraction solvents are fundamentally volatile compounds acquired from non-renewable resources, i.e petroleum-based solvents are presumed to be harmful to both human health and the environment. Owing to the new emphasis on environmental and safety protections and the development of green chemistry, finding alternative solvents to replace the organic ones has recently become a major concern. Indeed, there is a great interest in the scientific community to develop a suitable green approach to allow the extraction and recovery of the bioactive phytonutrients from berry sources for applications in improving human health and nutrition. In this study, the phytonutrient composition of three popular wild berries: blueberry (Vaccinium angustifolium), partridgeberry (Vaccinium vitis-idaea L.) and Rosehipberry (Rosa canina), were evaluated following extraction using biphasic green solvents at pH 2.5, 7.0, and 11.5 under pressurized conditions using Accelerated Solvent Extraction (ASE) system. The total phenolic content and composition, antioxidant activity, vitamin and mineral content of the berry extracts were evaluated using Folin-Ciocalteu assay, Ferric Reducing Antioxidant Power Assay (FRAP), Ultra-High-pressure Liquid Chromatography-Mass Spectrometry (UHPLC-MS) and inductively coupled plasma-mass spectrometry (ICP-MS), respectively. The highest total antioxidant activity (p ≤ 0.05) and phenolic content were observed in rosehip berry followed by blueberry and partridgeberry in the hydroethanolic extracts at pH 11.5. Nevertheless, the highest extraction efficiency of total fat-soluble vitamins (FSV) and total B vitamins were also observed in the hydroethanolic extract at pH 11.5. Both in rosehipberry and partridgeberry the highest vitamin C content was observed in hydroethanolic extract at pH 11.5, whereas in blueberry it was observed in the pH 2.5 hydroethanolic extract. In the present study, results demonstrated that using the green solvent system (hydroethanolic, 70:30 v/v) at alkaline pH (11.5) as a pressurized fluid in the ASE system provided significant recovery of phytonutrients from wild berries. This green environmentally friendly system of extraction could represent a suitable alternative for the preparation of food grade or green solvent-based extracts for applications in the food and nutraceutical industry.

Nonaqueous Solvent Extraction for Enhanced Metal Separations: Concept, Systems, and Mechanisms.

Efficient and sustainable separation of metals is gaining increasing attention, because of the essential roles of many metals in sustainable technologies for a climate-neutral society, such as rare earths in permanent magnets and cobalt, nickel, and manganese in the cathode materials of lithium-ion batteries. The separation and purification of metals by conventional solvent extraction (SX) systems, which consist of an organic phase and an aqueous phase, has limitations. By replacing the aqueous phase with other polar solvents, either polar molecular organic solvents or ionic solvents, nonaqueous solvent extraction (NASX) largely expands the scope of SX, since differences in solvation of metal ions lead to different distribution behaviors. This Review emphasizes enhanced metal extraction and remarkable metal separations observed in NASX systems and discusses the effects of polar solvents on the extraction mechanisms according to the type of polar solvents and the type of extractants. Furthermore, the considerable effects of the addition of water and complexing agents on metal separations in terms of metal ion solvation and speciation are highlighted. Efforts to integrate NASX into metallurgical flowsheets and to develop closed-loop solvometallurgical processes are also discussed. This Review aims to construct a framework of NASX on which many more studies on this topic, both fundamental and applied, can be built.

Relation between solubility and microextraction recovery data of lamotrigine for prediction of partitioning properties

The aim of this investigation was to study the solubility behavior of lamotrigine (LTG) as a model for basic drugs in the components of solvent systems used for a binary solvent dispersive liquid- liquid microextraction (BS-DLLME). In this system, chloroform (CLF) and dichloromethane (DCM) were used as the binary extracting agents and acetonitrile (ACN) and acetone (ACTN) were used as disperser solvents. Solubility of LTG were measured in the binary mixed solvents of ACN + water, ACTN + water and dry and water saturated mixtures of DCM + CLF at 298.2 K. Furthermore, two solvent mixtures including CLF, DCM, ACN and CLF, DCM, ACTN in various percentages were used to investigate the best solvents composition for extraction of LTG from aqueous samples. The solubility and recovery results were mathematically correlated by the Jouyban-Acree model and the accuracies of this model were evaluated by computing MRD%. The overall MRD% of 7.6% obtained for solubility data and 2.1% for recovery data show the capability of the Jouyban-Acree model for numerical representation of solubility and recovery profiles. Finally, it was tried to find a relation between solubility and recovery data to predict the partitioning of a drug between different liquids and exploring the appropriate solvent system for extraction from aqueous samples via DLLME procedure.

Characterisation of Parameters Influencing the Phase Separation in Copper Solvent Extraction Systems Using Oxime-Type Extractants for the Field Operation

Solvent extraction (SX) is one of the most widely applied hydrometallurgical processes in copper production from oxide ore. As the high-grade ore deposits have been developed and depleted, now only low-grade ore deposits are being developed and are therefore facing obstacles of extreme processing conditions. This results in leaching gangue minerals and requires a more complicated solvent extraction system. Recently, synergistic solvent extraction has been introduced to separate copper from the leached solution with high impurities. However, operational obstacles arise due to the complicated solvent extraction process, including multi-stages of extraction, and using more than one extractant in a single solvent extraction system. The phase separation in solvent extraction is one of the major issues in field operation. A poor phase separation could affect the entire process and eventually cause production loss. Therefore, in this study, the phase separation behaviours were studied in consideration of the field operation. Major parameters considered in the study were the type of diluent, temperature, mixing speed, solution pH and Oxidation Reduction Potential (ORP), and addition of impurities (flocculant and colloidal silica). The phase separation behaviours in the continuous counter-current SX system using a pilot-scale mixer-settler in the above conditions was investigated.

Leveraging slow DOTA f-element complexation kinetics to enable separations by kinetic design

The design of metal-concerned solvent extraction systems frequently leverages thermodynamically derived differences in selectivity. An alternative approach, leveraging kinetic control, has been considered much less seriously. Our recent manuscript describing DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) complexation kinetics across the lanthanide series shows the observed rate constant steadily increases across the series, with some non-monotonic behavior observed at terbium and thulium. This contrasts the thermodynamic stability constant trend, where lanthanide-DOTA stability constants initially increase and then plateau as a function of ionic radii after samarium. To leverage the kinetic differences of DOTA with the lanthanides across the series, kinetically based separations must be utilized. Since DOTA has very slow complexation kinetics, a separations system must expedite DOTA-metal complexation to allow a separation approximating practical application. In this report, a DOTA-based solvent extraction system, where DOTA is the aqueous holdback reagent and bis-2,4,4-trimethylpentylphosphinic acid (Cyanex 272) is the organic phase extractant, is demonstrated and compares the separations chemistry of Nd, Eu and Am. The slowness of DOTA complexation was addressed by heating the system. Results showed, in general, separation between metals is better during early phase contact, and diminishes under longer contact times. Under all conditions, separations are better than would be predicted based on a thermodynamic basis. This report suggests that while slowly complexing ligands classically used for biological applications may not be appropriate for thermodynamically designed metal separations, their use for kinetically based systems may be appropriate and enable a new design basis for f-element separations.

Selective separation of lithium from the high magnesium brine by the extraction system containing phosphate-based ionic liquids

The new extraction system containing phosphate-based ionic liquid ([N 1888 ][P 507 ] + TBP+FeCl 3 ) could significantly reduce the striping acidity from 6–9 mol·L −1 to 1~1.5 mol·L –1 . At the same time, the Li + extraction efficiency and separation factor were 63.8% and 190.7, respectively. • For the new system, Li + could be effectively stripped by HCl (1~1.5 mol·L −1 ). • The optimal results of E (Li) and β (Li/Mg) were 63.8% and 190.7, respectively. • The E (Li) remained above 70% by six extraction-stripping-extraction cycles. The high acidity of stripping is one of the major problems that hinder the industrialization of the tributyl phosphate (TBP) + FeCl 3 system for lithium extraction from the salt lake brines with high Mg/Li ratio. In this study, a novel solvent extraction system, trialkylmethylammonium di(2-ethylhexyl)orthophosphinate ([N 1888 ][P 507 ]) + TBP + FeCl 3 , was developed to significantly reduce the difficulty of stripping and simplify the extraction process. The conditions of extraction and stripping were systematically studied in the present work. The results showed that Li + extraction efficiency could reach 61% under the optimal extraction parameters and Li + stripping ratio was 90% with a relative mild conditions of O/A = 10:1, [HCl] aq = 1.5 mol·L –1 . Also, combined with experimental results, FT-IR analysis, and UV analysis, the possible mechanisms of lithium extraction and stripping were put forward. Li + was extracted from the aqueous phase through the formation of [Li·2TBP][FeCl 4 ] adduct, meanwhile [N 1888 ][P 507 ] was just slightly involved in the extraction step. In the stripping procedure, the interaction between [FeCl 4 ] − and [Li·2TBP] + might be destroyed, and new possible complexes, [Li·2TBP] + , and [FeCl 4 ·TBP·P 507 ] 2− /[FeCl 4 ·P 507 ] 2− were formed in the organic phase. Additionally, the extraction efficiency of Li + remained above 70% while the organic phase was reused for six cycles. Compared with the traditional system, the addition of [N 1888 ][P 507 ] resulted in a slight decrease of Li + extraction efficiency (about 5%), the stripping acidity significantly reduced from 6 mol·L –1 HCl to 1.5 mol·L –1 HCl. This new extraction system showed a promising performance in selective extracting and easy stripping in lithium separation from the salt lake brines with high Mg/Li ratio.

Insights into non-aqueous solvent extraction of gadolinium and neodymium from ethylene glycol solution using Cyanex 572

Comparison of the separation factors for Gd(III) over Nd(III) extraction from aqueous and non-aqueous ethylene glycol solutions using Cyanex 572 in kerosene. • Addition of water bridges the gap between hydrometallurgy and solvometallurgy. • Extraction of Gd(III) and Nd(III) from non-aqueous solution was compared with aqueous solution. • Gd and Nd extraction increases with increasing Cyanex 572 extractant concentrations. • Temperature had almost no effect on the extraction of both metal ions. • Under certain conditions, maximum separation factor was obtained and reached 22.09. The reprocessing of rare earth elements (REEs) by conventional hydrometallurgical processes remains a challenge because of the difficulties of separation. Solvometallurgy is a new non-aqueous solvent extraction approach including two immiscible organic phases which has been advanced for the extraction of rare earths. The less polar organic phase (LP) was a solution of Cyanex 572 (Cy-572) as an acidic extractant dissolved in kerosene. Whereas, the more polar organic phase (MP) was ethylene glycol with a limited amount of water dissolved in metal nitrate salts and lithium nitrate as a salting-out agent. The extraction of Gd(III) and Nd(III) from ethylene glycol solution was compared with extraction from an aqueous solution. The solvent extraction equilibrium was estimated by slope analysis method, and the composition of the Gd(III) extracted species in the less polar phase was proposed to be Gd(OH) L 2 . 2 HL ¯ . The non-aqueous system performs better separation of rare earths than the corresponding conventional extraction system. Subsequently, 0.1 mol/L HCl is the best stripping agent for both metal ions after two steps from the less polar phase, while a solution composed of 10% HF + 0.05 mol/L HCl is superior for nearly complete separation between the two elements. Eventually, the separation of binary mixtures of Gd(III) and Nd(III) is possible by this new non-aqueous solvent extraction system. A complete flow sheet process including extraction, scrubbing and stripping steps for the separation of Gd(III) and Nd(III) was proposed.

Citrus Flavonoids from Citrus reticulata Peels Potentially Target an Autophagy Modulator, MAP1LC3A, in Breast Cancer

Citrus flavonoids have been known for their vast biological activities including chemoprevention activities. However, the organic solvent extraction system limits its potential utilization. We recently adopted a hydrodynamic-cavitation method to extract citrus flavonoids from citrus peels. In this study we verified the high flavonoid content of the hydrodynamic-cavitation extract from Citrus reticulata peels and explore the potency of its citrus flavonoid contents as targeted chemoprevention agent for breast cancer by using bioinformatics. Based on a thin layer chromatography, the extract positively yielded high content of citrus flavonoids represented by hesperidin. The toxicity analysis by Protox II Online Tool revealed that hesperidin as the major citrus flavonoid in the extract was considered safe with a predicted LD50 of 12,000 mg/kg. We then further exploring citrus flavonoids’ capacity in targeting MAP1LC3A, a key protein in autophagy. UALCAN analysis validated that low expression of MAP1LC3A is associated with low survival rates in breast cancer patients. Limonin, hesperidin, narirutin, neohesperidine, and naringin are flavonoids from citrus peels that predicted to have inhibitory activity against Protein Kinase A (PKA), a negative upstream of MAP1LC3A, calculated by KNIME. Citrus flavonoids scoparone, cirsimaritin, 4',5,7-trimethoxyflavone, eupatorine, and hesperidin were also exhibit similar structure to an agonist of ATG4B, a protein that plays a role in MAP1LC3A activation. Furthermore, eupatorine, hesperidin, and cirsimaritin displayed a high affinity to ATG4B based on a molecular docking. We concluded that citrus flavonoids from citrus peels are safe to normal cells, and the citrus flavonoids potentially targets MAP1LC3A by inhibiting PKA and acting as ATG4B agonists. Thus, this extract-contained flavonoids from citrus peels is potential to be investigated further as a chemoprevention agent by inducing autophagy, especially for breast cancer.Keywords: Citrus reticulata, citrus flavonoid, autophagy, MAP1LC3A, breast cancer.