World Congress on Biosensors 2014

World Congress on Biosensors 2014
Biosensors 2014

Wednesday, 25 July 2012

Just Published: Journal of Chromatography A


A new issue of this journal has just been published. To see abstracts of the papers it contains (with links through to the full papers) click here:
Journal of Chromatography A
Selected papers from the latest issue:

New theory for distribution of minimum resolution in multi-component separations with noise/detection limits

25 July 2012, 10:20:58
Publication year: 2012
Source:Journal of Chromatography A, Volume 1251
Joe M. Davis
Equations were proposed recently for computing the distribution of minimum resolution (resolution distribution) of two Gaussian peaks with equal standard deviations, when peak heights in a multi-component separation follow a statistical distribution. The computation depended on the survival function of the peak-height ratio. Previously, an equation was derived for a first-order survival function that excluded peaks with heights less than a noise/detection limit. Here, an equation is derived for a corrected survival function, under the more realistic assumption that two minimally resolved peaks are lost if the height of their shoulder is less than the noise/detection limit. First-order and corrected survival functions and resolution distributions are derived for the exponential and uniform distributions of peak heights, and a corrected survival function and resolution distribution are derived for the log-normal distribution (LND) to complement a previous first-order derivation. Large peak losses (up to 99.3% of the noise/detection limit) are considered to find significant differences between the first-order and corrected resolution distributions. For the LND and exponential distribution, the corrected resolution distribution has slightly greater density in the low-resolution region but otherwise differs little from its first-order counterpart, unless the scale parameter of the LND is small (e.g. 0.75). For the uniform peak-height distribution, the corrected resolution distribution has higher density in the high-resolution region. The first-order and corrected resolution distributions are almost the same as long as the first moment of the first-order resolution distribution is greater than 0.6. The predictions are confirmed by Monte–Carlo simulation.

Highlights

► The distribution of resolution was computed for two peaks with random heights. ► Log-normal, exponential, and uniform peak-height distributions were investigated. ► The exclusion of peaks from distributions by a noise or detection limit was examined. ► Two exclusion criteria, based on peak height and shoulder height, were used. ► Both criteria predicted similar distributions except for small peak-height ranges.

Stir frit microextraction: An approach for the determination of volatile compounds in water by headspace-gas chromatography/mass spectrometry

25 July 2012, 10:20:58
Publication year: 2012
Source:Journal of Chromatography A, Volume 1251
M. Roldán-Pijuán, M.C. Alcudia-León, R. Lucena, S. Cárdenas, M. Valcárcel
In this article, a novel extraction approach, called stir frit microextraction (SFME), is presented. The new approach combines the extractive capability of a commercial polyethylene frit (20μm of pore size) with the stirring in the same device. The proposed extraction procedure allows the determination of benzene, toluene, ethylbenzene, xylene isomers and styrene (BTEX-S) in water samples. The analytes are extracted on the frit, previously conditioned with methanol, under continuous magnetic stirring. Once the extraction is performed, the frit is transferred to a headspace vial where the volatile compounds are desorbed from the frit (90°C, 30min) in a headspace module and analyzed by gas chromatography/mass spectrometry. Headspace conditions (time and temperature) as well as extraction conditions (ionic strength, type of stirring, extraction time, stirring rate and sample volume) have been systematically evaluated. The method was characterized on the basis of its linearity, sensitivity and precision. Limits of detection were in the range from 18ng/L (o-xylene) to 65ng/L (benzene). The repeatability of the proposed method, expressed as relative standard deviation (RSD) varied between 3.8% (toluene) and 8.2% (m- and p-xylene). The recovery study carried out in different water samples provided an average recovery of 94%, which demonstrated the applicability of the stir frit microextraction for the analytical problem selected in this article.

Highlights

► Stir frit microextraction combines extraction and stirring in the same device. ► A raw polyethylene frit is employed as sorptive material. ► The proposed extraction procedure allows the determination of BTEX-S from waters. ► The limits of detection were in the nanogram per liter range with good precision.

A multi-residue method for pesticides analysis in green coffee beans using gas chromatography–negative chemical ionization mass spectrometry in selective ion monitoring mode

25 July 2012, 10:20:58
Publication year: 2012
Source:Journal of Chromatography A, Volume 1251
Ionara R. Pizzutti, Andre de Kok, Carmem Dickow Cardoso, Bárbara Reichert, Marijke de Kroon, Wouter Wind, Laís Weber Righi, Rosselei Caiel da Silva
In this study, a new gas chromatography–mass spectrometry (GC–MS) method, using the very selective negative chemical ionization (NCI) mode, was developed and applied in combination with a modified acetonitrile-based extraction method (QuEChERS) for the analysis of a large number of pesticide residues (51 pesticides, including isomers and degradation products) in green coffee beans. A previously developed integrated sample homogenization and extraction method for both pesticides and mycotoxins analysis was used. An homogeneous slurry of green milled coffee beans and water (ratio 1:4, w/w) was prepared and extracted with acetonitrile/acetic acid (1%), followed by magnesium sulfate addition for phase separation. Aliquots from this extract could be used directly for LC–MS/MS analysis of mycotoxins and LC-amenable pesticides. For GC–MS analysis, a further clean-up was necessary. C18- and PSA-bonded silica were tested as dispersive solid-phase extraction (d-SPE) sorbents, separate and as a mixture, and the best results were obtained using C18-bonded silica. For the optimal sensitivity and selectivity, GC–MS detection in the NCI-selected ion monitoring (SIM) mode had to be used to allow the fast analysis of the difficult coffee bean matrix. The validation was performed by analyzing recovery samples at three different spike concentrations, 10, 20 and 50μgkg−1, with 6 replicates (n =6) at each concentration. Linearity (r 2) of calibration curves, estimated instrument and method limits of detection and limits of quantification (LOD i , LOD m , LOQ i and LOQ m , respectively), accuracy (as recovery %), precision (as RSD%) and matrix effects (%) were determined for each individual pesticide. From the 51 analytes (42 parent pesticides, 4 isomers and 5 degradation products) determined by GC–MS (NCI-SIM), approximately 76% showed average recoveries between 70–120% and 75% and RSD≤20% at the lowest spike concentration of 10μgkg−1, the target method LOQ. For the spike concentrations of 20 and 50μgkg−1, the recoveries and RSDs were even better. The validated LOQ m was 10, 20 and 50μgkg−1 for respectively 33, 3 and 6 of the analytes studied. For five compounds, the European Union method performance requirements for the validation of a quantitative method (average recoveries between 70-120% and repeatability RSD≤20%) were not achieved and 4 problematic pesticides (captan, captafol, folpet and dicofol) could not be detected as their parent compound, but only via their degradation products. Although the matrix effect (matrix-enhanced detector response) was high for all pesticides studied, the matrix interference was minimal, due to the high selectivity obtained with the GC–NCI-MS detection. Matrix-matched calibration for applying the method in routine analysis is recommended for reliable quantitative results.

Highlights

► A selective GC–MS (NCI-SIM) method and modified QuEChERS method were developed. ► An efficient slurry method for homogenization of green coffee beans was used. ► Clean-up sorbents were tested and C18-bonded silica was optimal. ► Validation was performed at spike concentrations of 10, 20 and 50μgkg−1 (n =6, at each level). ► Accuracy, precision, matrix effect, linearity, LOD and LOQ were assessed.

A new 1-hexyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate ionic liquid based ultrasound-assisted emulsification microextraction for the determination of organic ultraviolet filters in environmental water samples

25 July 2012, 10:20:58
Publication year: 2012
Source:Journal of Chromatography A, Volume 1251
Dandan Ge, Hian Kee Lee
A novel microextraction approach termed ionic liquid based ultrasound-assisted emulsification microextraction (IL-USAEME) combined with high-performance liquid chromatography-ultraviolet (HPLC-UV) was developed for the preconcentration and detection of organic ultraviolet (UV) filters in environmental water samples. An ionic liquid (IL) was used in place of an organic solvent as in conventional USAEME. In the study, orthogonal array designs (OAD) were employed for the optimization of the extraction parameters: type of IL, pH of the sample, extraction volume, ultrasonic time and salt concentration. In the first step, a mixed level OAD matrix, OA16 (41 ×212) was employed for the initial optimization. Based on the results of the first step, an ultra-hydrophobic IL, 1-hexyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate was chosen as the IL extractant and sample pH was set at a value of 3. Ultrasonic time, extraction volume and salt concentration were further optimized in the second step by an OA16 (45) matrix. Under the latter optimized conditions, calibration curves with coefficients of estimation higher than 0.997 over the concentration range of 5 and 1000ng/ml, and the relative standard deviations for six replicates of the extraction from 2.6 to 6.6% were obtained. The limits of detection for four organic UV filters were between 0.5 and 1ng/ml. The validated technique was applied to the analysis of organic UV filters in environmental water samples.

Highlights

► Ionic liquid, [HMIM][FAP], was used as a novel extractant in USAEME. ► Orthogonal array designs were employed for optimization of extraction parameters. ► Simple, fast and efficient method with good linearity, low LODs and %RSDs.

Cloud point–dispersive μ-solid phase extraction of hydrophobic organic compounds onto highly hydrophobic core–shell Fe2O3@C magnetic nanoparticles

25 July 2012, 10:20:58
Publication year: 2012
Source:Journal of Chromatography A, Volume 1251
Dimosthenis L. Giokas, Qing Zhu, Qinmin Pan, Alberto Chisvert
A novel two-step extraction technique combining cloud point extraction (CPE) with dispersive micro-solid phase extraction (D-μ-SPE) is presented in this work for the first time. The method involves initial extraction of the target analytes by CPE in the micelles of a non-ionic surfactant medium; then highly hydrophobic polysiloxane-coated core–shell Fe2O3@C magnetic nanoparticles (MNPs) are used to retrieve the micellar phase. In that manner, the micellar phase containing the analytes is the target of the D-μ-SPE step rather than the analytes directly. MNPs are then collected by the application of an adscititious magnetic field overcoming the need for specific steps associated with CPE such as centrifugation to separate the surfactant-rich phase, refrigeration of the condensed micellar phase to reduce its viscosity or appropriate apparatus that enable direct sampling of the surfactant-rich phase. A noteworthy feature of the method is the introduction of highly oleophilic MNPs, which afford rapid and quantitative mass transfer of the surfactant phase, as opposed to other more conventional hydrophobic nanoparticles. In that manner, fast and reproducible extraction is accomplished, lending improved analytical features compared to conventional CPE, such as reduced analysis time and relative inertness to surfactant concentration and equilibration temperature. The analytes were recovered from the surface of MNPs by ultrasound-assisted back-extraction in a water-immiscible organic solvent where analytes are readily partitioned but the surfactant has limited solubility, thus minimizing its interference during chromatographic detection. As an analytical demonstration, different UV absorbing chemicals with various physico-chemical properties were used as model organic compounds for optimizing the parameters associated with this novel two-step extraction approach. The proposed method, combining two different and efficient techniques, offers satisfactory analytical features in terms of repeatability (4.5–7.5%), reproducibility (7.0–14.9%) and accuracy (88.5–97.2%). Most importantly it poses as an alternative and fast method for sample pretreatment opening new insights in surfactant-mediated extractions.

Highlights

► Cloud point extraction is combined with dispersive micro-solid phase extraction. ► Highly hydrophobic magnetic nanoparticles are used to rapidly collect the micelles. ► Cloud point extraction is applied as a microscale sample preparation method. ► The method minimizes certain limitations and simplifies the CPE procedure.

Solid-phase extraction combined with dispersive liquid–liquid microextraction, fast derivatisation and high performance liquid chromatography–tandem mass spectrometry analysis for trace determination of short-chained dodecyl alcohol ethoxylates and dodecyl alcohol in environmental water samples

25 July 2012, 10:20:58
Publication year: 2012
Source:Journal of Chromatography A, Volume 1251
Agnieszka Zgoła-Grześkowiak, Tomasz Grześkowiak
A new method was developed for preconcentration, derivatisation and analysis of short-chained dodecyl alcohol ethoxylates and dodecyl alcohol. Solid-phase extraction combined with dispersive liquid–liquid microextraction was used for preconcentration of target compounds. Several parameters were optimised including different solid phase extraction sorbents, type and volume of both extracting and dispersive solvents. As a result fast and relatively simple preconcentration method was developed. The analytes were preconcentrated 700 times with the use of small sample volume. The target compounds were derivatised before analysis with the use of newly developed procedure. The derivatisation procedure was made in vial insert and was performed at room temperature with the use of 1-naphthoyl chloride as the derivatisation agent. The developed method was used for the analysis of short-chained dodecyl alcohol ethoxylates and dodecyl alcohol in both sewage effluent from sewage treatment plants and river water samples.

Highlights

► We have developed a new isolation procedure for dodecyl alcohol and its ethoxylates. ► We have developed a new derivatisation procedure in microlitre volumes. ► We have determined target compounds in samples from sewage effluents and river water.

Optimization of solvent bar microextraction combined with gas chromatography mass spectrometry for preconcentration and determination of tramadol in biological samples

25 July 2012, 10:20:58
Publication year: 2012
Source:Journal of Chromatography A, Volume 1251
Ensieh Ghasemi
A simple, rapid and sensitive analytical method for preconcentration and determination of tramadol in different biological samples have been developed using solvent bar microextraction (SBME) combined with gas chromatography–mass spectrometry (GC–MS). The target drugs were extracted from 12ml of aqueous sample with pH 12.0 (source phase; SP) into an organic extracting solvent (n-nonanol) located inside the pores and lumen of a polypropylene hollow fiber (receiving phase; RP). In order to obtain high extraction efficiency, the effect of different variables on the extraction efficiency was studied using an experimental design. The variables of interest were the type of organic phase, pH of the source phases, ionic strength, volume of the source phase, stirring rate, extraction time and temperature. The experimental parameters of SBME were optimized using a Box–Behnken design (BBD) after a Plackett–Burman screening design. The detection limits were 0.02μgL−1 with 4.5% RSD (n =5, c =10μgL−1) for tramadol. Finally, the applicability of the proposed method was evaluated by extraction and determination of the drugs in different biological samples. The results indicated that SBME method has excellent clean-up and high-preconcentration factor and can be served as a simple and sensitive method for monitoring of tramadol in the biological samples.

Highlights

► SBME–GC–MS was applied for preconcentration and determination of tramadol. ► The experimental parameters were optimized using chemometric design. ► Under optimum conditions, the high preconcentration factor was obtained. ► The SBME was successfully applied for analysis of tramadol in biological samples.

Optimization for speed and sensitivity in capillary high performance liquid chromatography. The importance of column diameter in online monitoring of serotonin by microdialysis

25 July 2012, 10:20:58
Publication year: 2012
Source:Journal of Chromatography A, Volume 1251
Jing Zhang, Yansheng Liu, Andrea Jaquins-Gerstl, Zhan Shu, Adrian C. Michael, Stephen G. Weber
The speed of a separation defines the best time resolution possible in online measurements using chromatography. The desired time resolution multiplied by the flow rate of the stream of analyte being sampled defines the maximum volume of sample per injection. The best concentration sensitivity in chromatography is obtained by injecting the largest volume of sample that is consistent with achieving a satisfactory separation, and thus measurement accuracy. Taking these facts together, it is easy to understand that separation speed and concentration sensitivity are linked in this type of measurement. To address the problem of how to achieve the best sensitivity and shortest measurement time simultaneously, we have combined recent approaches to the optimization of the separation itself with an analysis of method sensitivity. This analysis leads to the column diameter becoming an important parameter in the optimization process. We use these ideas in one particular problem presented by online microdialysis sampling/liquid chromatography/electrochemical detection for measuring concentrations of serotonin in the dialysate. In this case the problem becomes the optimization of conditions to yield maximum signal for a given sample volume under the highest speed conditions with a certain required number of theoretical plates. It turns out that the observed concentration sensitivity at an electrochemical detector can be regulated by temperature, particle size, injection volume/column diameter, and void time. The theory was successfully used for optimization of neurotransmitter serotonin measurement by capillary HPLC when sampling from a microdialysis flow stream. The final conditions are: 150μm i.d., 3.1cm long columns with 1.7μm particle diameter working at a flow rate of 12μL/min, an injection volume of 500nL, and a temperature of 343K. The retention time for serotonin is 22.7s, the analysis time is about 36s (which allows for determination of 3-methoxytyramine), and the sampling time is about 0.8min with a perfusion flow rate of 0.6μL/min.

Highlights

► Our goal is system optimization for speed and concentration sensitivity. ► Concentration sensitivity depends on the injection volume. ► There is an optimum column diameter for a given injection volume. ► T, d p , V inj /d c , and t 0 regulate concentration sensitivity for a required N a . ► Serotonin (∼0.5nM) in microdialysate samples (0.5μL) in less than 30s.

Nano-scale liquid chromatography/mass spectrometry and on-the-fly orthogonal array optimization for quantification of therapeutic monoclonal antibodies and the application in preclinical analysis

25 July 2012, 10:20:58
Publication year: 2012
Source:Journal of Chromatography A, Volume 1251
Xiaotao Duan, Lipeng Dai, Shang-Chiung Chen, Joseph P. Balthasar, Jun Qu
Therapeutic monoclonal antibodies (mAbs) constitute a group of highly effective agents for treating various refractory diseases. Nonetheless it is challenging to achieve selective and accurate quantification of mAb in pharmaceutical matrices, which is required by PK studies. Liquid chromatography/mass spectrometry under selected reaction monitoring mode (LC/SRM-MS) is emerging as an attractive alternative to immunoassays because of the high specificity and multiplexing capacity it provides, but may fall short in terms of sensitivity, reliability and quantitative accuracy. Moreover, the strategy for optimization of the MS conditions for many candidates of signature peptides (SP) and the selection of the optimal SP for quantification remains elusive. In this study, we employed a suite of technical advances to overcome these difficulties, which include: (i) a nano-LC/SRM-MS approach to achieve high analytical sensitivity, (ii) a high-resolution nano-LC/LTQ/Orbitrap for confident identification of candidate peptides, (iii) an on-the-fly orthogonal array optimization (OAO) method for the high-throughput, accurate and reproducible optimization for numerous candidate peptides in a single LC/MS run without using synthesized peptides, (iv) a comprehensive evaluation of stability of candidates in matrix using the optimized SRM parameters, (v) the use of two unique SP for quantification of one mAb to gauge possible degradation/modification in biological system and thus enhancing data reliability (e.g. rejection of data if the deviation between the two SP is greater than 25%) and (vi) the utilization of purified target protein as the calibrator to eliminate the risk of severe negative biases that could occur when a synthesized peptide is used as calibrator. To show a proof of concept, this strategy is applied in the quantification of cT84.66, a chimeric, anti-CEA antibody, in preclinical mouse models. A low detection limit of the mAb down to 3.2ng/mL was achieved, which is substantially more sensitive than established immunoassay methods for anti-CEA antibodies. The quantitative method showed good linearity (within the range of 12.9ng/mL to 32.3μg/mL in plasma), accuracy and precision. Additionally, the ultra-low sample consumption (2μL plasma per preparation) permits the acquisition of an entire set of time course data from the same mouse, which represents a prominent advantage for PK study using small-animal models. The developed method enabled an accurate PK investigation of cT84.66 in mice following intravenous and subcutaneous administrations at relatively low doses over an extended period of time. The strategy employed in this study can be easily adapted to the sensitive and accurate analysis of other mAb and therapeutic proteins.

Highlights

► OAO procedure allowed for rational selection of optimal signature peptide and high-throughput method development. ► The use of nano-LC/MS enabled highly sensitive quantification of mAb in plasma. ► The use of two unique SP and protein calibrator enhanced quantitative accuracy. ► The extremely low sample consumption is desirable for small-animal models. ► The method provided superior selectivity and sensitivity over immunoassays.

Tetraazacalix[2]arene[2]triazine modified silica gel: A novel multi-interaction stationary phase for mixed-mode chromatography

25 July 2012, 10:20:58
Publication year: 2012
Source:Journal of Chromatography A, Volume 1251
Wenjie Zhao, Wenjing Wang, Hong Chang, Shiwei Cui, Kai Hu, Lijun He, Kui Lu, Jinxia Liu, Yangjie Wu, Jiang Qian, Shusheng Zhang
A novel multi-interaction and mixed-mode stationary phase based on tetraazacalix[2]arene[2]triazine modified silica (NCS) was synthesized and characterized by infrared spectra, elemental analysis and thermogravimetric analysis. Mechanism involved in the chromatographic separation is the multi-interaction including hydrophobic, π–π, hydrogen-bonding, inclusion and anion-exchange interactions. Based on these interactions, successful separation could be achieved among polycyclic aromatic hydrocarbons, aromatic position isomers, organic bases and phenols in reversed-phase chromatography. Inorganic anions were also shown to be individually separated in anion-exchange chromatography by using the same column. Moreover, the results here also demonstrated that NCS based stationary phase could effectively reduce the adverse effect of residual silanol in the separation process. Such stationary phase with characteristics of multi-interaction mechanism and mixed-mode separation is potential for the analysis of complex samples.

Highlights

► Tetraazacalix[2]arene[2]triazine was first utilized as a selector in chromatography. ► Multiple retention mechanism was involved in the chromatographic separation. ► The new material is a mixed-mode reversed-phase/anion-exchange phase. ► Tetraazacalix[2]arene[2]triazine can effectively mask the residual silanols.

Preparation and evaluation of poly(4-vinylphenylboronic acid-co-pentaerythritol triacrylate) monolithic column for capillary liquid chromatography of small molecules and proteins

25 July 2012, 10:20:58
Publication year: 2012
Source:Journal of Chromatography A, Volume 1251
Hui Huang, Zian Lin, Yao Lin, Xiaobo Sun, Yanyan Xie, Lan Zhang, Guonan Chen
A mixed-mode monolithic stationary phase was prepared for capillary liquid chromatography (cLC) by in situ copolymerization of 4-vinylphenylboronic acid (VPBA) and pentaerythritol triacrylate (PETA) in a binary porogenic solvent consisting of ethylene glycol/cyclohexanol. The monomer of VPBA functioned as ion-exchange sites, hydrophilic ligands, hydrophobic groups and affinity sites, while PETA was introduced as a hydrophilic crosslinker. The resultant monoliths with different column properties (e.g. morphology, permeability and selectivity) were optimized by adjusting the ratio of VPBA to PETA and the composition of porogenic solvent. The results showed that the selectivity of the monoliths increased with increasing content of VPBA in the polymerization mixture. A series of alkylbenzenes, amides, and anilines were used to evaluate the column performance in terms of hydrophobic, hydrophilic and cation-exchange interactions. At an optimized flow rate of 50μL/min (corresponding to 0.265mm/s), the monolith exhibited high column efficiencies of 43,000–100,000plates/m for alkylbenzenes. Good repeatability was obtained with relative standard deviation (RSD) of retention factor (k) less than 0.65% for run-to-run (n =5) and less than 2.49% for column-to-column (n =5). In addition, the poly(VPBA-co-PETA) monolithic column was applied to the separation of phenols, nucleobases, and proteins, respectively. These successful applications demonstrate the purposed monoliths are promising for cLC separation of small molecules and proteins.

Highlights

► A mixed-mode poly(VPBA-co-PETA) monolithic column is prepared via single-step in situ polymerization. ► It can be applied to the separation of a series of small molecules and proteins. ► The purposed monolith exhibits high separation ability and selectivity.

High-performance liquid chromatography enantioseparation of atropisomeric 4,4′-bipyridines on polysaccharide-type chiral stationary phases: Impact of substituents and electronic properties

25 July 2012, 10:20:58
Publication year: 2012
Source:Journal of Chromatography A, Volume 1251
Paola Peluso, Victor Mamane, Emmanuel Aubert, Sergio Cossu
The high performance liquid chromatography (HPLC) enantioseparation of eleven atropisomeric 4,4′-bipyridines was performed in the normal and polar organic phase mode using three cellulose-based chiral stationary phases (CSPs), namely Lux® Cellulose-1, Lux® Cellulose-2, Lux® Cellulose-4, and two amylose-based CSPs, Chiralpak® AD-H and Lux® Amylose-2. n-Hexane/2-propanol mixtures and pure ethanol were employed as mobile phases. The combined use of Chiralpak® AD-H and Lux® Cellulose-2 allowed to enantioseparate all the considered bipyridines. Ten bipyridines were enantioseparated at the multimilligram level allowing the elution sequence determination of the enantiomers as well as their future use for the preparation of homochiral metal organic frameworks (MOFs). Moreover, the performance of the CSPs regarding the same bipyridine was different and dependent on the backbone as well as on the side chain of the polymer. The impact of substitution pattern, shape and electronic properties of the molecules on the separation behavior was investigated through the evaluation of retention factors (k), separation factors (α), resolution (R s) and molecular properties determined using density functional theory (DFT) calculations. In this regard, the substituents at the 3,3′,5,5′ positions of the 4,4′-bipyridyl rings exhibited a pivotal role on the enantioseparation.

Highlights

► Chiralpak AD-H and Lux Cellulose-2 allowed to enantioseparate 4,4′-bipyridines. ► Ten out of eleven bipyridines were enantioseparated at the multimilligram level. ► Impact of substituents and electronic properties on enantioseparation is discussed.

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