Ionic-liquid/Carbowax 20 M functionalized capsule phase microextraction platform for the extraction of phosphodiesterase-5 inhibitors from human serum and urine prior to their determination by LC-MS.

Capsule phase microextraction (CPME) is an efficient bioanalytical technique that streamlines the sample preparation by integrating the filtration and stirring mechanism directly into the device. A novel composite sorbent designed to be selective towards the target analytes consisting of mixed-mode sorbent chemistry synthesized by sol-gel technology is found promising and superior to the conventional C18 sorbents. Herein we describe the encapsulation of an ionic liquid (IL)/Carbowax 20M-functionalized sol-gel sorbent (sol-gel IL/Carbowax 20 M) in the lumen of porous polypropylene tubes for the capsule phase microextraction of three phosphodiesterase-5 inhibitors namely avanafil, sildenafil, and tadalafil in human serum and urine samples. The CPME device was characterized by Scanning Electron Microscopy (SEM) and Fourier-Transform Infrared Spectroscopy (FT-IR). The experimental parameters of CPME procedure (e.g. sample pH and ionic strength, extraction time, stirring rate, elution solvent and volume) were carefully optimized to achieve the highest possible extraction efficiency for the analytes. Method validation was conducted in terms of precision, linearity, accuracy, matrix effect, lower limits of quantification, and limits of detection (LOD). The method linearity was investigated in the range of 50-1000 ng mL-1 for all analytes while the precision was less than 11.8 % in all cases. For all analytes, the LOD values were 17 ng mL-1. The IL/CW 20M-functionalized microextraction capsules could be reused at least 25 times both for urine and serum samples. The green character and the applicability of the proposed method were evaluated using the ComplexGAPI and BAGI indexes. The optimized CPME protocol exhibited reduced consumption of organic solvent and generation of waste, cost-effectiveness, and simplicity. Finally, the proposed method was successfully applied to the analysis of sildenafil in human urine after administration of drug-containing formulation.

A novel headspace solid-phase microextraction arrow method employing comprehensive two-dimensional gas chromatography-mass spectrometry combined with chemometric tools for the investigation of wine aging.

BACKGROUND: Omics is used as an analytical tool to investigate wine authenticity issues. Aging authentication ensures that the wine has undergone the necessary maturation and developed its desired organoleptic characteristics. Considering that aged wines constitute valuable commodities, the development of advanced omics techniques that guarantee aging authenticity and prevent fraud is essential. RESULTS: Α solid phase microextraction Arrow method combined with comprehensive two-dimensional gas chromatography-mass spectrometry was developed to identify volatiles in red wines and investigate how aging affects their volatile fingerprint. The method was optimized by examining the critical parameters that affect the solid phase microextraction Arrow extraction (stirring rate, extraction time) process. Under optimized conditions, extraction took place within 45 min under stirring at 1000 rpm. In all, 24 monovarietal red wine samples belonging to the Xinomavro variety from Naoussa (Imathia regional unit of Macedonia, Greece) produced during four different vintage years (1998, 2005, 2008 and 2015) were analyzed. Overall, 237 volatile compounds were tentatively identified and were treated with chemometric tools. Four major groups, one for each vintage year were revealed using the Hierarchical Clustering Analysis. The first two Principal Components of Principal Component Analysis explained 86.1% of the total variance, showing appropriate grouping of the wine samples produced in the same crop year. A two-way orthogonal partial least square - discriminant analysis model was developed and successfully classified all the samples to the proper class according to the vintage age, establishing 17 volatile markers as the most important features responsible for the classification, with an explained total variance of 88.5%. The developed prediction model was validated and the analyzed samples were classified with 100% accuracy according to the vintage age, based on their volatile fingerprint. SIGNIFICANCE: The developed methodology in combination with chemometric techniques allows to trace back and confirm the vintage year, and is proposed as a novel authenticity tool which opens completely new and hitherto unexplored possibilities for wine authenticity testing and confirmation.

Utilization of a pH-switchable hydrophilicity solvent for the microextraction of clomipramine from human urine samples.

Clomipramine (CLP) is a tricyclic antidepressant drug, and its determination in biological samples is of high importance in clinical and forensic evaluations to assure appropriate drug concentrations. In the present study, benzoic acid was employed as a pH-switchable hydrophilicity solvent (SHS) for the microextraction of CLP from authentic human urine samples prior to its determination by high performance liquid chromatography-ultraviolet detection (HPLC-UV). The microextraction protocol was based on the phase transition of the SHS through pH alteration that resulted in its rapid dispersion and simultaneous phase separation. The obtained solid was collected in a syringe filter, dissolved in methanol, and analyzed. The main parameters that affected the efficiency of the microextraction procedure were studied and optimized to ensure high extraction efficiency for CLP and the analytical method was validated. Under optimum conditions, good linearity was observed between 0.05 and 5.0 µg mL-1. The limit of detection and limit of quantification were found to be 0.015 and 0.05 µg mL-1, respectively. The RSD values for intra-day repeatability and inter-day precision were 2.4-8.9 % and 1.7-9.1 %, respectively. The relative recovery values were within 90.0 and 110.0 % in all cases, demonstrating good method accuracy. The proposed SHS microextraction showed cost-efficiency, handling simplicity, and rapidity resulting in enhanced sample throughput. Moreover, the proposed method exhibited a green character and good applicability based on its evaluation by Green Analytical Procedure Index and Blue Applicability Grade Index.

A flow-batch lab-in-syringe foam microextraction platform for the simultaneous preconcentration and in situ membraneless gas-liquid separation of mercury prior to cold vapor atomic absorption spectrometry.

Herein, the proof-of-concept of a novel lab-in-syringe (LIS) foam microextraction platform is presented as a front-end to cold vapor atomic absorption spectrometry (CVAAS) for the simultaneous preconcentration and membraneless gas-liquid separation (GLS) of inorganic mercury in biological samples. The proposed method is based on the on-line formation of the ammonium pyrrolidine dithiocarbamate complex with mercury that was retained in the pores of polyurethane foam immobilized on the piston of the LIS system. Metal complex elution and in situ mercury vapor generation are accomplished inside the microsyringe in a flow-batch format, while the separation of vapor species is achieved via the membraneless GLS found at the top of the syringe's barrel. Under optimized operation conditions, for 90 s preconcentration time, the limit of detection was 0.02 µg L-1 and the repeatability (RSD) was 3.8% (at the 0.5 µg L-1 concentration level), within a working range extending up to 4.0 µg L-1. The practicality of the novel manifold was demonstrated using the Blue Applicability Grade Index, while the accuracy of the method was evaluated using certified reference materials and spiked samples.

A continuous flow polyurethane foam solid phase microextraction lab-in-syringe platform for the automatic determination of toxic metals.

A novel fully automatic continuous flow polyurethane foam solid phase microextraction lab-in-syringe system for on-line sample preconcentration/separation has been developed as a front-end to flame atomic absorption spectrometry. For the first time lab-in-syringe in continuous flow has been adopted for the determination of toxic metals. The microextraction procedure was performed after on-line metal complexation with ammonium pyrrolidine dithiocarbamate, while the elution was conducted by 400 µL of methyl isobutyl ketone. The main chemical and hydrodynamic factors that affected the performance of the method were optimized using Cd and Pb as model analytes. For 90 s preconcentration time, the limits of the detection were 0.20 and 1.7 µg L-1 for Cd and Pb, respectively, while the enhancement factors were 79 for Cd and 150 for Pb. The relative standard deviation% values were lower than 2.8 % for all analytes. As a proof-of-concept the proposed system was used for environmental water analysis, providing relative recoveries within the range of 94.0 and 104.4 %. The Green Analytical Procedure Index and Blue Applicability Grade Index proved reduced environmental impact and high practicality for the proposed method.

Fabricating a designer capsule phase microextraction platform based on sol-gel Carbowax 20M-zwitterionic ionic liquid composite sorbent for the extraction of lipid-lowering drugs from human urine samples.

A sol-gel Carbowax 20 M/3-[(3-Cholamidopropyl) dimethyl ammonio]-1-propanesulfonate composite sorbent-based capsule phase microextraction device has been fabricated and characterized for the determination of four statins (pravastatin, rosuvastatin, pitavastatin, and atorvastatin) in human urine. The presence of ionizable carboxyl functional groups in statins requires pH adjustment of the sample matrix to ensure that the target molecules are in their protonated form (pH should be 2 units below their pKa values) which not only is cumbersome but also risks unintended contamination of the sample. This challenge was addressed by introducing zwitterionic ionic liquid in addition to neutral, polar Carbowax 20 M polymer in the sol-gel-derived composite sorbent. As such, the composite zwitterionic multi-modal sorbent can simultaneously extract neutral, cationic, and anionic species. This particular attribute of the composite sorbent eliminates the necessity of the matrix pH adjustment and consequently simplifies the overall sample preparation workflow. Various experimental parameters such as the sample amount, extraction time, salt addition, stirring rate, and elution solvent type that may affect the extraction performance of the statins were investigated using a central composite design and the one-parameter-at-a-time approach. The analytes and the internal standard were separated on a C18 column with gradient elution using phosphate buffer (20 mM, pH 3) and acetonitrile as mobile phase. The analytes were detected at 237 nm. The method was validated, and linearity was observed in the range 0.10-2.0 µg mL-1 for all compounds. The method precision was better 9.9% and 10.4% for intra-day and inter-day, respectively, while the relative recoveries were acceptable, ranging between 83.4 and 116% in all cases. Method greenness was assessed using the ComplexGAPI index. Finally, the method's applicability was demonstrated in the determination of the statins in authentic human urine after oral administration of pitavastatin and rosuvastatin-containing tablets.

A review of bioanalytical applications of microextraction techniques combined with derivatization.

Microextraction techniques have attracted the attention of many researchers working in the field of bioanalysis due to their unique advantages, mainly in downsizing the scale of sample preparation steps. In parallel, analytical derivatization offers a powerful combination in terms of additional sensitivity, selectivity and compatibility with modern separation techniques. The aim of this review is to discuss the most recent advances in bioanalytical sample preparation based on the combination of microextraction and analytical derivatization. Both innovative fundamental reports and analyte-targeted applications are included and discussed. Dispersive liquid-liquid extraction and solid-phase microextraction are the most common techniques that typically combined with derivatization, while the development of novel and greener protocols is receiving substantial consideration in the field of analytical chemistry.

An integrated automatic lab-in-syringe sol-gel coated foam microextraction platform as a front-end to high performance liquid chromatography for the migration studies of bisphenol A.

The proof-of-concept of an integrated automatic foam microextraction lab-in-syringe (FME-LIS) platform coupled to high performance liquid chromatography is presented. Three different sol-gel coated foams were synthesized, characterized, and conveniently packed inside the glass barrel of the LIS syringe pump, as an alternative approach for sample preparation, preconcentration and separation. The proposed system efficiently combines the inherent benefits of lab-in-syringe technique, the good features of sol-gel sorbents, the versatile nature of foams/sponges, as well as the advantages of automatic systems. Bisphenol A (BPA) was used as model analyte, due to the increasing concern for the migration of this compound from household containers. The main parameters that affect the extraction performance of the system were optimized and the proposed method was validated. The limit of detection for BPA were 0.5 and 2.9 µg L-1, for a sample volume of 50 mL and 10 mL, respectively. The intra-day precision was <4.7% and the inter-day precision was <5.1% in all cases. The performance of the proposed methodology was evaluated for the migration studies of BPA using different food simulants, as well as for the analysis of drinking water. Good method applicability was observed based on the relative recovery studies (93-103%).

Design and development of second-generation fabric phase sorptive extraction membranes: Proof-of-concept for the extraction of organophosphorus pesticides from apple juice prior to GC-MS analysis.

In this work, different sol-gel sorbent-coated second-generation fabric phase sorptive extraction (FPSE) membranes were synthesized using titania-based sol-gel precursors. The proposed membranes were tested for their efficiency to extract eleven selected organophosphorus pesticides (OPPs) from apple juice samples. Among the examined materials, sol-gel C18 coated titania-based FPSE membranes showed the highest extraction efficiency. These membranes were used for the optimization and validation of an FPSE method prior to analysis by gas chromatography-mass spectrometry. The detection limits for OPPs ranged between 0.03 and 0.08 ng mL-1. Moreover, the relative standard deviation was < 8.2% and 8.4% for intra-day and inter-day studies, respectively. The relative recoveries were 91-110% (intra-day study) and 90-106% (inter-day study) for all the target analytes, demonstrating good overall method accuracy. Moreover, the novel membranes were reusable at least 5 times. The titania-based membranes were compared to the conventional silica-based membranes and their utilization resulted in higher extraction recoveries.

Investigating the applicability of polar fabric phase sorptive extraction for the HPLC quantitation of salivary vitamin B12 following administration of sublingual tablets and oral sprays.

In this study, a simple and rapid fabric phase sorptive extraction (FPSE) protocol combined with high performance liquid chromatography-ultraviolet detection (HPLC-UV) was developed for the monitoring of salivary vitamin B12 levels. Different sol-gel coated cellulose and polyester membranes were evaluated and sol-gel Carbowax 20 M coated polyester membranes were chosen for the selective extraction of the target analyte from saliva samples. Face-centered central composite design (FC-CCD) was employed for the investigation and optimization of sample volume, extraction time and stirring rate, while the other experimental factors were investigated using the classical one-factor-at-a- time" (OFAT) method. Validation of the FPSE-HPLC-UV method was conducted according to the FDA guidelines for bioanalytical methodologies. The lower limit of quantification for vitamin B12 was 0.10 µg mL-1 and the linear range was 0.10-10.0 µg mL-1. The relative recoveries for intra-day and inter-day studies were 87.5-113.8% and 88.2-119.2%, respectively. The relative standard deviation was better than 8.2% in all cases, demonstrating good method precision. The sol-gel Carbowax 20 M coated FPSE membranes were found to be reusable for up to 25 times. Finally, the proposed scheme was successfully employed for the quantitation of salivary vitamin B12 at different time points following the administration of sublingual tablets and oral sprays.

Sol-Gel Graphene Oxide-Coated Fabric Disks as Sorbents for the Automatic Sequential-Injection Column Preconcentration for Toxic Metal Determination in Distilled Spirit Drinks.

Sol-gel graphene oxide-coated polyester fabric platforms were synthesized and used for the on-line sequential injection fabric disk sorptive extraction (SI-FDSE) of toxic (i.e., Cd(II), Cu(II) and Pb(II)) metals in different distilled spirit drinks prior to their determination by electrothermal atomic absorption spectrometry (ETAAS). The main parameters that could potentially influence the extraction efficiency of the automatic on-line column preconcentration system were optimized and the SI-FDSE-ETAAS method was validated. Under optimum conditions, enhancement factors of 38, 120 and 85 were achieved for Cd(II), Cu(II) and Pb(II), respectively. Method precision (in terms of relative standard deviation) was lower than 2.9% for all analytes. The limits of detection for Cd(II), Cu(II) and Pb(II) were 1.9, 7.1 and 17.3 ng L-1, respectively. As a proof of concept, the proposed protocol was employed for the monitoring of Cd(II), Cu(II), and Pb(II) in distilled spirit drinks of different types.

Solid-phase microextraction Arrow combined with comprehensive two-dimensional gas chromatography-mass spectrometry for the elucidation of the volatile composition of honey samples.

In this work, a solid-phase microextraction (SPME) Arrow method combined with comprehensive two-dimensional gas chromatography-mass spectrometry (GC × GC-MS) was developed for the elucidation of the volatile composition of honey samples. The sample preparation protocol was optimized to ensure high extraction efficiency of the volatile organic compounds (VOCs) which are directly associated with the organoleptic properties of honey and its acceptance by the consumers. Following its optimization, SPME Arrow was compared to conventional SPME in terms of sensitivity, precision, and number of extracted VOCs. The utilization of SPME Arrow fibers enabled the determination of 203, 147, and 149 compounds in honeydew honey, flower honey, and pine honey, respectively, while a significantly lower number of compounds (124, 94, and 111 for honeydew honey, flower honey, and pine honey, respectively) was determined using conventional SPME. At the same time, the utilization of SPME Arrow resulted in enhanced sensitivity and precision. All things considered, SPME Arrow and GC × GC-MS can be considered as highly suitable for the elucidation of the volatile composition of complex food samples resulting in high sensitivity and separation efficiency.

A simple and green liquid chromatography method for the determination of ibuprofen in milk-containing simulated gastrointestinal media for monitoring the dissolution studies of three-dimensional-printed formulations.

A fast and green ultra-high-performance liquid chromatographic method was developed for the determination of ibuprofen in milk-containing simulated gastrointestinal media to monitor the dissolution of three-dimensional printed formulations. To remove interfering compounds, protein precipitation using methanol as a precipitation reagent was performed. The separation of the target analyte was performed on a C18 column using a mobile phase consisting of 0.05% v/v aqueous phosphoric acid solution: methanol, 25:75% v/v. Method validation was conducted using the total error concept. The ß-expectation tolerance intervals did not exceed the acceptance criteria of ±15%, meaning that 95% of future results will be included in the defined bias limits. The relative bias ranged between ─1.1 and +3.2% for all analytes, while the relative standard deviation values for repeatability and intermediate precision were less than 2.8% and 3.9%, respectively. The achieved limit of detection was 0.01 µg/ml and the lower limit of quantitation was established as 2 µg/ml. The proposed method was simple, and it required reduced organic solvent consumption following the requirements of Green Analytical Chemistry. The method was successfully employed for the determination of ibuprofen in real biorelevant media obtained from dissolution studies.

Dual Lab-in-Syringe Flow-Batch Platform for Automatic Fabric Disk Sorptive Extraction/Back-extraction as a Front End to Inductively Coupled Plasma Atomic Emission Spectrometry.

A novel dual lab-in-syringe flow-batch (D-LIS-FB) platform for automatic fabric-disk-in-syringe sorptive extraction followed by oxidative back-extraction as a front end to inductively coupled plasma atomic emission spectrometry (ICP-AES) is presented for the first time. Sol-gel poly(caprolactone)-poly(dimethylsiloxane)-poly(caprolactone)-coated polyester fabric disks were packed at the top of the glass barrel of a microsyringe pump as an alternative to column preconcentration. Herein lie multiple significant advantages including effectiveness, compactness, lower back-pressure, and lower time of analysis. Copper, lead, and cadmium were used as model analytes for the exploration of the capabilities of the developed platform. The online retained metal-diethyldithiophosphate complexes were eluted using diisopropyl ketone prior to atomization. Undesirable incompatibility of organic solvents for direct injection into the ICP-AES system was overcome ingeniously in a flow manner by oxidative back-extraction of the analytes utilizing a second lab-in-syringe setup. Following its optimization, the D-LIS-FB platform showed excellent linearity, in combination with good method precision (i.e., RSD < 3.4%) and trueness. Moreover, the limits of detection were 0.25 µg L-1 for Cd(II), 0.13 µg L-1 for Cu(II), and 0.37 µg L-1 for Pb(II), confirming the applicability of the proposed system for metal analysis at trace levels. As a proof-of-concept, the developed versatile system was utilized for the analysis of different environmental, food, and biological samples.

Designing an "all-in-one" microextraction capsule device for the liquid chromatographic-fluorescence determination of doxorubicin and its metabolites in rat plasma.

In this study, an "all-in-one" microextraction device was designed and fabricated for the extraction of doxorubicin and its two metabolites from rat plasma prior to their determination by high performance liquid chromatography coupled to fluorescence detector. A sol-gel-based sorbent was synthesized in situ and incorporated within two conjoined porous polypropylene tubes together with a cylindrical magnetic bar in order to avoid the need of an external stirring bar. Among other sorbents investigated, the moderately polar sol-gel poly(tetrahydrofuran) was found to be advantageous due to its high affinity toward the target analytes. Systematic investigation of the critical parameters affecting the adsorption and the desorption step was carried out. Due to the "built-in" filtration mechanism of the porous microextraction capsules, the isolation of the analytes was performed directly in the plasma matrix without any previous sample pretreatment (i.e., protein precipitation, centrifugation, etc.). The proposed method was validated in terms of linearity, accuracy, precision, specificity, sensitivity, and stability according to the FDA guidelines. The limits of detection ranged between 1 - 2 ng mL-1 while the lower limits of quantitation of the analytes were calculated as 10 ng mL-1. The accuracy (% relative error) was found within -9.7 - 15.3% under both intra- and inter-day conditions. The precision was better than 13.4% in all cases. ComplexGAPI index was employed to present the green attributes of the developed protocol from the preparation of the microextraction device to the final determination of the analytes. Finally, the applicability of the fabricated stand-alone extraction device was demonstrated in the analysis of the target analytes in rat plasma after intravenous administration of doxorubicin in order to assess its pharmacokinetic profile.

Determination of bisphosphonate active pharmaceutical ingredients in pharmaceuticals and biological materials: An updated review.

Although almost 60 years have passed since their first application, bisphosphonates are still in use as medicine against osteoporosis. Due to their chemical structures and properties, these compounds have attracted the attention of many scientists. From an analytical point of view, various analytical methods have been published in the last decade for the determination of these drugs involving separation techniques (HPLC, GC, CE), electrochemical, sensors, spectrophotometry, IR, etc. The present article is a continuation of the 2008 review article of the authors on the analysis of bisphosphonates (C.K. Zacharis, P.D. Tzanavaras, JPBA 48 (2008) 483-496) and it focuses on bioanalytical and pharmaceutical QC applications on the analysis of this class of pharmaceutically active compounds presenting a critical discussion on advantages/disadvantages, figures of merit and analytical features of techniques and methods on this topic.

Development and Validation of an HPLC-UV Method for the Dissolution Studies of 3D-Printed Paracetamol Formulations in Milk-Containing Simulated Gastrointestinal Media.

Herein, a simple and rapid HPLC method for the determination of paracetamol milk-containing biorelevant media is proposed. The separation of the analyte from the milk-containing biorelevant media was accomplished isocratically using a mobile phase containing 25 mM phosphate buffer (pH = 3.0) and methanol, 80:20, v/v at a flow rate of 1 mL min-1. Following a protein precipitation-based sample clean-up, a thorough investigation of the effect of the precipitation reagent (methanol, acetonitrile, 10% v/v trifluoroacetic acid solution) on the analyte recovery was performed. The matrix effect was assessed in each biorelevant medium by comparing the slopes of the calibration curves of aqueous and matrix-matched calibration curves. The method was comprehensively validated using the accuracy profiles. The ß-expectation tolerance intervals did not exceed the acceptance criteria of ±15%, meaning that 95% of future results will be included in the defined bias limits. The relative bias ranged between -4.5 and +3.9% for all analytes, while the RSD values for repeatability and intermediate precision were less than 2.7% and 3.0%, respectively. The achieved limit of detection (LOD) was 0.02 µg mL-1 and the lower limits of quantitation (LLOQ) were established as 10 µg mL-1, which corresponded to 2% of the highest expected concentration of paracetamol. The proposed scheme was utilized for the determination of paracetamol in dissolution studies of its 3D-printed formulation in milk-containing biorelevant media.

Exploring the volatile profile of whiskey samples using solid-phase microextraction Arrow and comprehensive two-dimensional gas chromatography-mass spectrometry.

We present a novel sample preparation method for the extraction and preconcentration of volatile organic compounds from whiskey samples prior to their determination by comprehensive two-dimensional gas chromatography (GC × GC) coupled to mass spectrometry (MS). Sample preparation of the volatile compounds, important for the organoleptic characteristics of different whiskeys and their acceptance and liking by the consumers, is based on the use of the solid-phase microextraction (SPME) Arrow. After optimization, the proposed method was compared with conventional SPME regarding the analysis of different types of whiskey (i.e., Irish whiskey, single malt Scotch whiskey and blended Scotch whiskey) and was shown to exhibit an up to a factor of six higher sensitivity and better repeatability by a factor of up to five, depending on the compound class. A total of 167 volatile organic compounds, including terpenes, alcohols, esters, carboxylic acids, ketones, were tentatively-identified using the SPME Arrow technique, while a significantly lower number of compounds (126) were determined by means of conventional SPME. SPME Arrow combined with GC × GC-MS was demonstrated to be a powerful analytical tool for the exploration of the volatile profile of complex samples, allowing to identify differences in important flavour compounds for the three different types of whiskey investigated.

An automatic on-line sol-gel pyridylethylthiopropyl functionalized silica-based sorbent extraction system coupled to flame atomic absorption spectrometry for lead and copper determination in beer samples.

A novel sol-gel pyridylethylthiopropyl functionalized silica-based sorbent was synthesized and utilized in an on-line column preconcentration system coupled with flame atomic absorption spectrometry for metal determination. The developed platform was used for the determination of Pb(II) and Cu(II) in beer samples, since there are limited automatic methods for routine analysis of alcoholic beverage. For a preconcentration time of 60 s, the calculated enhancement factors were 96 for Cu(II) and 130 for Pb(II). The limits of detection were 0.33 µg L-1 and 1.98 µg L-1 for Cu(II) and Pb(II), respectively. Moreover, the RSDs were less than 2.9% indicating good method precision. The method was successfully employed for the analysis of commercially available beers. The Cu(II) content of the samples was 1.6-21.8 µg L-1 and the Pb(II) content was 7.3-17.6 µg L-1. The developed manifold exhibited operational simplicity and good performance characteristics, indicating its potential utilization for routine analysis in beer industry.