Silica Capillary Research Articles

Eco-Friendly Capillary Electrophoresis Method for the Quantification of Apixaban in Oral Dosage Form

The present work describes, for the first time, an eco-friendly capillary zone electrophoresis (CZE) methodology for determining apixaban (APX), an oral anticoagulant. Separation was carried out using a fused silica capillary with an applied voltage of 20 kV and hydrodynamic injection for 5 s at 50 mbar. The electrolyte system consisted of 50 mM sodium borate at pH 8.0. The method was validated as recommended by ICH, establishing selectivity, linearity, precision, accuracy, and robustness. The analytical procedure was linear in the range of 10–125 µg mL−1 (r = 0.999). The limits of detection and quantification were determined to be 1.77 µg mL−1 and 5.37 µg mL−1, respectively. Precision was evaluated by relative standard deviation (RSD), with an intra-day RSD (n = 6) of 0.96% and an inter-day RSD (n = 18) of 4.42%. The average recovery rates for the pharmaceutical samples were excellent, ranging from 98.03% to 101.01%, with an RSD of 1.51%. Moreover, the green profile of the method was evaluated using the National Environmental Methods Index (NEMI), Analytical Eco-Scale, Green Analytical Procedure Index (GAPI), and Analytical GREEnness Metric (AGREE) assessment tools. The results suggest that the CZE method aligns with the principles of green chemistry, offering a greener alternative for the routine analysis of APX quality control. Also, the method presents a low-cost analysis, using fewer organic solvents and minimizing waste generation compared to techniques commonly used in routine analysis.

Novel Pinhole Emitter Chip for Micro Supercritical Fluid Chromatography-Mass Spectrometry with Integrated Dilution-Free Fluidic Back-Pressure Regulation.

We present a novel chip-based device featuring a pinhole emitter for mass spectrometry (MS) coupling with integrated fluidic back-pressure regulation for supercritical mobile phases. This design enables facile coupling of packed capillary columns used for supercritical fluid chromatography (SFC) with atmospheric pressure ionization mass spectrometry. The monolithic microfluidic chips were fabricated using selective laser-induced etching, seamlessly integrating multiple functions, including comb-shaped particle retention structures for column packing and ports for zero-clearance connection with standard fused silica capillaries. The integrated restrictive pinhole MS emitter generated by dielectric breakdown is a key innovation of the micro SFC-MS platform. It enables a controlled decompression of the supercritical CO2-based mobile phase within few micrometers to efficiently transfer the analytes from the compressed supercritical fluid into the ambient gas phase in front of the MS orifice. The inclusion of an arrowhead-shaped fluidic element further enables precise, dilution-free back-pressure regulation. With a minimal postcolumn volume of just 3 nL, the system shows excellent MS coupling performance, as demonstrated by rapid SFC-MS analysis of pharmaceuticals and natural products.

Determination of Biogenic Amines in Foods by Capillary Electrophoresis

This review article intends to provide comprehensive analysis on biogenic amines, their source, type and classification. Biogenic amines are nitrogen containing organic compound that naturally exits in nature. They have low molecular weight and are basic in nature. They are active components that act as precursors for synthesis of alkaloids, hormones, protein, nucleotides and aromatic compounds. They occur in plants, animal and microorganism and play an essential role in metabolic and physiological function. This paper focuses on determination of biogenic amines in food by capillary electrophoresis as it causes several health problems such as histamine causes headache, digestive disorders and neurotoxicity, tyramine can cause hypertension and cadaverine can cause cytotoxixity. Biogenic amines are determined by several techniques such as high-performance liquid chromatography (HPLC), gas chromatography (GC), capillary electrophoresis (CE), Ion exchange chromatography. This paper further focuses on advantages of capillary electrophoresis in determination of biogenic amines in food. Capillary electrophoresis is a liquid phase separation method. The technique of capillary electrophoresis is used to identify, separate and quantify large range of components. There are several types of CE. Instrumentation of CE includes fused silica capillary which has length of 20 - 50cm. The reservoir is filled with separation buffer and the two ends of capillary tube extend between two reservoirs. CE has wide variety of application in identification, separation and quantification. In conclusion, biogenic amines cause many health hazard and is important to be identified and this paper deals with their presence and identifican in food.

Optical Determination of the Internal Capillary Diameter Used in Taylor Dispersion Analysis.

In this work, we describe an optical setup to determine the internal diameter of narrow bore fused silica capillary used in capillary electrophoresis and Taylor dispersion analysis (TDA). Indeed, fluctuations up to about±3-4µm on the capillary I.D. can generate important inaccuracy on the hydrodynamic radius determination by TDA. Calibration of the optical set-up, impact of the operator and of the placement of the capillary in the focal plane, and the influence of the way to cut the capillary were investigated and discussed. This optical set-up was next used to determine capillary I.D. on a 60 m long capillary spool. Relatively small variations were observed along a 60 m capillary spool (0.3µm maximum variation), while important I.D. fluctuations can be observed from capillary batch to batch. Taking three capillaries of three different nominal I.D. values, Rh values of sodium benzoate obtained by TDA were not significantly different if the capillary I.D. were optically measured, while significant variations were observed with the nominal I.D. values. A protocol based on TDA of sodium benzoate was proposed for calibrating narrow bore fused silica capillary I.D. without the use of optical measurements for researchers that would not have access to such optical equipment.

Experimental and molecular simulation of carbon dioxide solubility in hexadecane at varying pressures and temperatures

CO2-EOR can make underground storage efforts possible, addressing both energy demands and climate issues. This study establishes an in-situ method to measure the degree of CO2 solubility in hexadecane in a wide range of P-T conditions. CO2 and hexadecane with known volumes were mixed in silica capillaries and examined by Raman spectroscopy after reaching an equilibrium at certain P-T condition to establish a relationship between mole fraction of CO2 in hexadecane and ratio of Raman peak area. Results showed that solubility of CO2 decreases with increasing temperature and increases with pressure. Complementing the experimental data, hybrid grand canonical Monte Carlo/molecular dynamics (GCMC/MD) simulations were performed to study the swelling effect of CO2/hexadecane system and the diffusion of CO2 within hexadecane. Simulation results were validated against Raman spectroscopy and previously published CO2 solubility data, as well as a genetic algorithm-based (GA) predictive model, all matching with high accuracy and conforming each other. Based on molecular simulation results, the necessity of accounting for volumetric changes in solubility calculations to enhance the accuracy of predictive models in similar systems was revealed. Additionally, in contrast to temperature, the effect of pressure on the diffusion coefficient remains relatively minimal. Ultimately, this study provides solutions for in-situ probing techniques to determine the solubility of various fluids in a wide range of P-T conditions, processes supporting CO2-EOR and carbon storage operations underground.

Programmable C−N Bond Formation through Radical‐Mediated Chemistry in Plasma‐Microdroplet Fusion

AbstractNon‐thermal plasma discharge produced in the wake of charged microdroplets is found to facilitate catalyst‐free radical mediated hydrazine cross‐coupling reactions without the use of external light source, heat, precious metal complex, or trapping agents. A plasma‐microdroplet fusion platform is utilized for introduction of hydrazine reagent that undergoes homolytic cleavage forming radical intermediate species. The non‐thermal plasma discharge that causes the cleavage originates from a chemically etched silica capillary. The coupling of the radical intermediates gives various products. Plasma‐microdroplet fusion occurs online in a programmable reaction platform allowing direct process optimization and product validation via mass spectrometry. The platform is applied herein with a variety of hydrazine substrates, enabling i) self‐coupling to form secondary amines with identical N‐substitutions, ii) cross‐coupling to afford secondary amine with different N‐substituents, iii) cross‐coupling followed by in situ dehydrogenation to give the corresponding aryl‐aldimines with two unique N‐substitutions, and iv) cascade heterocyclic carbazole derivatives formation. These unique reactions were made possible in the charged microdroplet environment through our ability to program conditions such as reagent concentration (i. e., flow rate), microdroplet reactivity (i. e., presence or absence of plasma), and reaction timescale (i. e., operational mode of the source). The selected program is implemented in a co‐axial spray format, which is found to be advantageous over the conventional one‐pot single emitter electrospray‐based microdroplet reactions.

Programmable C-N Bond Formation through Radical-Mediated Chemistry in Plasma-Microdroplet Fusion.

Non-thermal plasma discharge produced in the wake of charged microdroplets is found to facilitate catalyst-free radical mediated hydrazine cross-coupling reactions without the use of external light source, heat, precious metal complex, or trapping agents. A plasma-microdroplet fusion platform is utilized for introduction of hydrazine reagent that undergoes homolytic cleavage forming radical intermediate species. The non-thermal plasma discharge that causes the cleavage originates from a chemically etched silica capillary. The coupling of the radical intermediates gives various products. Plasma-microdroplet fusion occurs online in a programmable reaction platform allowing direct process optimization and product validation via mass spectrometry. The platform is applied herein with a variety of hydrazine substrates, enabling i) self-coupling to form secondary amines with identical N-substitutions, ii) cross-coupling to afford secondary amine with different N-substituents, iii) cross-coupling followed by in situ dehydrogenation to give the corresponding aryl-aldimines with two unique N-substitutions, and iv) cascade heterocyclic carbazole derivatives formation. These unique reactions were made possible in the charged microdroplet environment through our ability to program conditions such as reagent concentration (i. e., flow rate), microdroplet reactivity (i. e., presence or absence of plasma), and reaction timescale (i. e., operational mode of the source). The selected program is implemented in a co-axial spray format, which is found to be advantageous over the conventional one-pot single emitter electrospray-based microdroplet reactions.

Superfine multiresonant fiber grating sensors assisted with silica capillaries

We propose and demonstrate a superfine multiresonant fiber grating sensor characterized by superior spectral resolution and enhanced sensing capabilities. This sensor can be easily constructed by inserting a tilted fiber Bragg grating (TFBG) probe into a silica capillary filled with a refractive index (RI) matching oil. As the fiber cladding, the RI-matching oil, and the capillary all have the same RI, the cladding modes excited by the TFBG can extend into the RI-matching oil and capillary, facilitating surface sensing outside the capillary. Our study shows that the number of cladding modes increases, and the resonance spectrum becomes denser as the outer diameter of the capillary gets larger. As a result, the detection accuracy of RI based on mode cutoff wavelength identification can be improved. Particularly, with a capillary diameter of 1 mm, the heightened spectral density enhances refractometric accuracy by nearly an order of magnitude compared to the intrinsic TFBG. The superfine multiresonant fiber grating sensor proposed here is flexible in configuration and easy to fabricate, providing a new strategy for developing new fiber sensing devices.

Simultaneous quantification of chlorogenic acid, quercetin, and kaempferol in Urceola rosea leaves by CE and HPLC techniques: method validation and comparative study

Two analytical methods, CE and HPLC, were developed, validated, and compared for simultaneously determining chlorogenic acid, quercetin, and kaempferol in Urceola rosea leaves collected from twelve different sources of Thailand. The determination was accomplished by CE on the uncoated fused silica capillary tube and by HPLC on the ZORBAX Eclipse Plus C18 column. Chlorogenic acid was found to have the highest average amount in U. rosea leaves, followed by kaempferol and quercetin, respectively. Compared to CE, HPLC is considered to provide higher sensitivity and robustness as indicated by lower LOD and LOQ values as well as % RSD of robustness for all analytes. Overall, the present study first demonstrated that both methods were selective, sensitive, and robust, allowing reliable simultaneous quantification of three major bioactive compounds in U. rosea leaves, which could be beneficially applied for quality control assessment of this plant material, particularly those cultivated in Thailand.

Simple simultaneous analysis of various cardiovascular drug mixtures with vincamine: comparative eco-friendly assessment

The development of two eco-friendly analytical methods for the simultaneous determination of eight cardiovascular drugs; hydrochlorothiazide (HCT), captopril (CPL), lisinopril (LSP), valsartan (VAL), atorvastatin (ATR), bisoprolol (BSL), amlodipine (AML) and carvedilol (CVL); alongside with the nutraceutical vincamine (VIC) is essential for sustainable pharmaceutical analysis. This study explores the application of Micellar Electro Kinetic Chromatography (MEKC) and High-Performance Liquid Chromatography (HPLC) for this purpose. In MEKC method, the separation was done using fused silica capillary (41.5 cm × 50 µm id) and a back ground electrolyte consisting of 50 mM borate buffer (pH 9) containing 50 mM sodium lauryl sulphate (SLS) and 10% organic modifier (Acetonitrile). In HPLC method, separation was performed on a ZORBAX Extend-C18 (4.6 × 250 mm, 5 µm) column, using a gradient mobile phase consisting of 50 mM phosphate buffer pH 3 and methanol. Both methods attained good linearity (r ≥ 0.9996) with low values of LOD and LOQ. Both methods were successfully applied in the determination of co-administered single, binary and ternary dosage form of the studied drugs. Moreover, application of various combinations of co-administered dosage forms was achieved in rat plasma, confirming the applicability of these methods in different matrices. The use of micellar solutions in MEKC enhances separation efficiency while reducing the need for organic solvents, aligning with green chemistry principles. HPLC methods were optimized using environmentally benign solvents, ensuring reduced toxicity and waste production. The methodologies were evaluated through green, white, and blue metrics to ensure comprehensive sustainability, considering ecological impact, safety, and practical efficiency. These methods were not only cost-effective and time-saving but achieved high efficiency, sensitivity, and reproducibility making them ideal for routine use in pharmaceutical analysis.

A simple method to remove polyimide coating from fused silica capillaries for capillary electrophoresis

A simple and cost-effective method for making capillary electrophoresis (CE) detection windows is reported. A low-cost laser engraving machine equipped with a 450 nm high-power blue laser was used to remove the polyimide coating from the fused silica capillary by laser scanning the desired section. The entire process is automated and controlled in real time by software. This method can be easily adopted by many CE users for routine practice and is scalable for high-throughput production of detection windows across multiple capillaries.

Investigation of induced electroosmotic flow in small-scale capillary electrophoresis devices: Strategies for control and reversal.

Electroosmotic flow (EOF) is the bulk flow of solution in a capillary or microchannel induced by an applied electric potential. For capillary and microchip electrophoresis, the EOF enables analysis of both cations and anions in one separation and can be varied to modify separation speed and resolution. The EOF arises from an electrical double layer at the capillary wall and is normally controlled through the pH and ionic strength of the background buffer or with the use of additives. Understanding and controlling the electrical double layer is therefore critical for maintaining acceptable repeatability during method development. Surprisingly, in fused silica capillaries at low pH, studies observe an EOF even though the capillary surface should be neutralized. Previous work has suggested the presence of an "induced electroosmotic flow" from radial electric fields generated across the capillary wall due to the separation voltage and grounded components external to the capillary. Using thin-wall (15µm) fused silica separation capillaries to facilitate the study of radial fields, we show that the EOF mobility depends on both the separation voltage and the location of external grounds. This is consistent with the induced EOF model, in which radial electric fields embed positive charges at the capillary walls to create an electrical double layer. The magnitude of the effect is characterized and shown to have long-range influences that are difficult to completely null by moving grounded components away from the separation capillary. Instead, active EOF control using externally applied potentials or a passive approach using a negative separation voltage are discussed as two possible methods for controlling the induced EOF. Both methods can reverse the EOF and improve the resolution and peak efficiency in amino acid separations.

Getting the Best out of Capillary Electrophoresis and Capillary Electrophoresis-Mass Spectrometry by Quantifying Sources of Peak Broadening for Proteins Using Polyelectrolyte Multilayer Coated Fused Silica Capillaries.

Capillary electrophoresis (CE) has emerged as a relevant technique for protein and biopharmaceutical analysis, as it combines high separation efficiency, sensitivity, and versatility. The use of capillary coatings, including successive multiple ionic-polymer layers (SMILs), reduces interactions between analytes and the capillary, further improving the CE performance. Nevertheless, separations done on SMIL coatings rarely surpass 500 × 103 plates/m. To obtain the best out of the CE, it is interesting to have a detailed look at the sources of peak dispersion. Separations of a mix of model proteins were performed on (poly(diallyldimethylammonium chloride)/poly(styrenesulfonate))2.5-coated capillaries at different electrical field strengths, leading to plate height H against migration velocity u plots that enabled a quantitative analysis of each contribution. Using this model, capillary lengths and injected volumes were systematically varied. For the first time, the contribution of sample electrophoretic heterogeneity to the total peak dispersion was deciphered for model proteins and a monoclonal antibody. Dispersion due to electromigration was seen to have an impact on plate heights in the case of triangular peaks of small molecules but not for proteins under the present conditions. UV and mass spectrometry detections were compared on the same capillary, providing valuable information on the impact of the detection type on separation efficiency. Close to 1 million plates/m were reached in the best conditions.

Preparation of DNA nanoflower-modified capillary silica monoliths for chiral separation.

Innovative chiral capillary silica monoliths (CSMs) were developed based on DNA nanoflowers (DNFs). Baseline separation of enantiomers such as atenolol, tyrosine, histidine, and nefopam was achieved by using DNF-modified CSMs, and the obtained resolution value was higher than 1.78. To further explore the effect of DNFs on enantioseparation, different types of chiral columns including DNA strand containing the complementary sequence of the template (DCT)-modified CSMs, DNF2-modified CSMs, and DNF3-modified CSMs were prepared as well. It was observed that DNF-modified CSMs displayed better chiral separation ability compared with DCT-based columns. The intra-day and inter-day repeatability of model analytes' retention time and resolution kept desirable relative standard deviation values of less than 8.28%. DNF2/DNF3-modified CSMs were able to achieve baseline separation of atenolol, propranolol, 2'-deoxyadenosine, and nefopam enantiomers. Molecular docking simulations were performed to investigate enantioselectivity mechanisms of DNA sequences for enantiomers. To indicate the successful construction of DNFs and DNF-modified CSMs, various charaterization approaches including scanning electron microscopy, agarose gel electrophoresis, dynamic light scattering analysis, electroosmotic flow, and Fourier-transform infrared spectroscopy were utilized. Moreover, the enantioseparation performance of DNF-modified CSMs was characterized in terms of sample volume, applied voltage, and buffer concentration. This work paves the way to applying DNF-based capillary electrochromatography microsystems for chiral separation.

Quantitative Measurement of Multiple Elements in Micro‐Quantities of Crude Oil Using In Situ Analysis by Laser Ablation‐ICP‐MS

Multi‐element quantification in small amounts of material and in situ measurements at the micrometre scale are essential aspects of geological sample investigation. A direct and rapid simultaneous multi‐elemental determination of metals in crude oil samples was carried out by combining direct laser ablation of the oil inserted in silica capillaries with inductively coupled plasma‐mass spectrometry. The accuracy of LA‐ICP‐MS determination was demonstrated by analysing CONOSTAN reference material oils, certified for multiple elements, and by comparing LA‐ICP‐MS measurement results with those obtained by ICP‐OES using microwave‐assisted sample digestion. The results obtained by both methods were in agreement with certified values. The LA‐ICP‐MS method showed an adequate precision with a mean relative standard deviation of less than 10% for multi‐element determination, and was sufficiently sensitive to determine the majority of elements. LA‐ICP‐MS was also applied to the determination of elements in crude oils of different origins. LA‐ICP‐MS is a good alternative method allowing the determination of elements in organic fluids (oil and bitumen) in shorter times, involving less material consumption, smaller test portion size and with higher throughput compared with protocols using, for instance, sample digestion. It validates the possible application of metal analysis in hydrocarbon‐containing fluid inclusions for metallogenic purposes.

Simultaneous Determination of Glycerol and Carbohydrates in Sweat by Capillary Electrophoresis with Amperometric Detection

Background: Glycerol, sucrose, lactose, glucose, and fructose are important biomarkers in human sweat because their contents can reflect physiological status and health conditions. It is of high importance to determine them in sweat for health monitoring, disease diagnosis, physical training, etc. Aim: The aim of this work is to develop a method based on capillary electrophoresis and amperometric detection for the simultaneous determination of glycerol and carbohydrates in sweat. Objective: A capillary electrophoretic method based on pipette-tip-based detection electrodes and micro-injectors was developed for the simultaneous determination of glycerol, sucrose, lactose, glucose, and fructose in sweat samples Method: Sweat samples diluted in the background electrolyte of 75 mM NaOH aqueous solution were electrokinetically introduced into a piece of separation capillary via pipette tip-based microinjectors. Glycerol, sucrose, lactose, glucose, and fructose were determined by capillary electrophoresis in combination with a pipette-tip-based copper electrode. Results: At a DC voltage of 12 kV, the capillary electrophoretic separation of the five analytes could be achieved in less than 11 min in a piece of 40 cm long fused silica capillary containing 75 mM NaOH aqueous solution. Linearity was observed between the currents and concentrations, with the limits of detection ranging from 0.21 to 0.72 µM at a detection potential of 0.65 V. Glycerol, sucrose, lactose, glucose, and fructose in sweat samples were positively identified and accurately measured. Conclusion: The method was successfully applied in the simultaneous determination of glycerol and carbohydrates in sweat samples with satisfactory assay results. It will find a wide range of applications in clinical diagnosis, health monitoring, and drug and food analysis.

Exploring a new format of thermophoretic measurement – Stop-flow microscale thermophoresis in the narrow-bore transparent capillary

The classic format of the microscale thermophoresis technique (MST) requires the use of disposable glass capillaries. Their total capacity significantly exceeds the volume of the sample used directly in the thermophoretic measurement. An alternative approach that allows for reducing the consumption of sample, reagents and elimination of waste is the use of narrow-bore capillaries, commonly applied in the capillary electrophoresis technique (CE), in combination with injecting sample segment of a reduced length. This article presents the first-ever use of a transparent and flexible narrow-bore capillary for this purpose, which is much easier to handle than a regular non-transparent silica capillary. In this approach, it is possible to perform thermophoretic analysis with a small sample volume, which is delivered to the detection site using pressure-induced flow, or electrophoretically – while simultaneously performing electrophoretic separation. We focused primarily on the former approach, called Transparent Capillary Stop-Flow MicroScale Thermophoresis (TCSF-MST). Its potential was demonstrated in systems presenting the original use of the thermophoresis phenomenon: monitoring the progress of the fluorescent derivatization reaction, determining the critical micellization concentration of a surfactant, and quantitative analysis of fluorophores based on the internal standard method. The obtained results suggest that the new format can be considered an interesting alternative to the traditional MST methodology, and also seems consistent with the idea of “​​green” and “white” analytical chemistry.

Simple and Fast Determination of Carbaryl Pesticide in Commercial Topical Formulations by Capillary Electrophoresis

A novel analytical method using capillary zone electrophoresis (CZE) for simple and fast determination of the pesticide carbaryl in commercial topical formulations was developed and validated. The carbaryl was previously hydrolyzed quantitatively under an alkaline medium (NaOH solution) to form 1-naphthol, which was separated and quantified by CZE with spectrophotometric detection at 214 nm. Optimization of the hydrolysis reaction regarding time and NaOH concentration was conducted. The CZE separation was achieved in less than 3 min using a bare silica capillary (60 cm total length) and a 10 mmol L-1 sodium borate buffer (pH 9.3) as background electrolyte. The proposed CZE method was linear in the 0.25 to 70 mg L-1 concentration range, as attested by a coefficient of determination (R2) higher than 0.999 and confirmed by the lack of fit test. Recovery tests at three concentration levels provided recovery percentages ranging from 80 to 115%, indicating acceptable accuracy. The limits of detection (LOD) and quantification (LOQ) were 0.08 and 0.25 mg L-1, respectively. The proposed CZE method was successfully applied for carbaryl determination in commercial samples of topical formulations such as powders and dry bath gel.

Simultaneous measurement of bidirectional magnetic field and temperature with a dual-channel sensor based on the whispering gallery mode

What we believe is a novel dual-channel whispering gallery mode (WGM) sensor for concurrently measuring bidirectional magnetic field and temperature is proposed and demonstrated. Two sensing microcavities [magnetic fluid (MF)-infiltrated capillary and polydimethylsiloxane (PDMS)-coated microbottle, respectively, referred as Channel 1 (CH1) and Channel 2 (CH2)] are integrated into a silica capillary to facilitate the dual-channel design. Resonant wavelengths corresponding to CH1 and CH2 mainly depend on the change in the magneto-induced refractive index and the change in the thermo-induced parameter (volume and refractive index) of the employed functional materials, respectively. The MF-infiltrated capillary enables bidirectional magnetic field sensing with maximum sensitivities of 46 pm/mT and -3 pm/mT, respectively. The PDMS-coated structure can realize the temperature measurement with a maximum sensitivity of 79.7 pm/°C. The current work possesses the advantage of bidirectionally magnetic tunability besides the temperature response, which is expected to be used in field such as vector magnetic fields and temperature dual-parameter sensing.

Electrochemical detection of cocaine metabolites (benzoylecgonine and ecgonine) at the miniaturized electrified liquid-liquid interface

The main urinary cocaine metabolites are benzoylecgonine and ecgonine methyl ester. These molecules possess two chemical functional groups that can be charged within the conventional pH range, this is the tertiary amine group (both) and the carboxylic group (benzoylecgonine). We have found that in the pH range from 2 to 6 (for benzoylecgonine) and pH from 2 to 4 (for ecgonine methyl ester) both molecules can be detected at the electrified liquid-liquid interface (eLLI) by following the interfacial ion transfer reactions triggered in the presence of the concerned metabolites in the aqueous phase. The presence of the benzene ring in the benzoylecgonine structure increases its hydrophobicity (on the formal Galvani potential difference scale) by around 200 mV as compared with ecgonine methyl ester which transfer is overlaid with the inorganic cations crossing the LLI at the positive end of the potential window. Macroscopic eLLI was used during physicochemical ecgonine methyl ester and benzoylecgonine characterization as we have defined their diffusion coefficients, ion partition, and concentration fraction diagrams (only for the latter). The miniaturized platform was used during electroanalytical studies focused on benzoylecgonine giving a few µM limit of detection. For this purpose, we have used the fused silica capillary as the eLLI support. All our findings allowed us to use this system first to develop the electroanalytical protocol for benzoylecgonine quantification to finally detect it in the spiked urine sample with nearly 100 % recovery.