In the second part of this review article, the recent progress in supercritical fluid chromatography (SFC) for enantiomeric separations is evaluated. With the substantial developments carried out over the past years in instrumentation, columns, and detector hyphenation, the interest in chiral SFC has been steadily growing in various fields. In combination with novel developments in chiral stationary phase chemistries, the enantioselective analysis range has been significantly extended. Several applications reported on the enantioselective separation of drugs and pharmaceutical compounds using chiral SFC are discussed, including pharmaceutical applications, clinical research, forensic toxicology, and environmental sciences.

Over the past decade, particularly since the commercialization of the first high-pressure and low-dispersion instruments, supercritical fluid chromatography (SFC) has become a more established technique.

Since the introduction of polar co-solvents as a mobile phase, SFC has been applied to various fields, ranging from fossil fuels and polymers to food and pharmaceutical applications. Chirality also plays a significant role in these research areas, as enantioselective separations are often required to discriminate between enantiomers showing different pharmacological or biological activities (1). Based on the advantages listed in part 1 of our review (2), it does not come as a surprise that an increased number of studies using SFC for chiral applications have been reported in the literature.

The instrumental improvements, such as pressure stability and UV-noise reduction, but also the commercialization of novel polar and nonpolar stationary phases, coated or immobilized on to smaller and superficially porous particles, have led to increased performance in chiral SFC analysis (3). These developments provide a powerful orthogonal and versatile analytical approach for high-efficient and high-throughput chiral assessments. Moreover, the developments in SFC–mass spectrometry (MS) have also strengthened the position of chiral SFC, especially when a certain level of sensitivity or additional selectivity is desired. In the past decade, SFC has been increasingly used for chiral analysis—most notably in the field of pharmaceutical analysis, clinical applications, forensic toxicology, and environmental analysis, as discussed in the following sections. The most significant requirements in those areas are speed (pharmaceutical), sensitivity (clinical, forensic toxicology, and environmental analysis), and selectivity (illicit drug analysis). The aforementioned unique properties of supercritical fluids and recent innovations in SFC can make an important contribution to tackling these challenges.

Due to the expected differences in pharmacological activity of enantiomers, the spatial configurations of new pharmaceutical compounds need to be thoroughly investigated in the drug development pipeline. Table 1 lists an overview of the pharmaceutical applications reported since 2015,
where SFC has been used for enantioselective separations (4,5). Similar to chiral liquid chromatography (LC)-based applications, polysaccharide-based chiral stationary phases (CSPs) have been most frequently employed. The broad applicability and high-loadability of these phases support their wide use in drug development. Only a few studies reported optimal separation using macrocyclic glycopeptides, cyclofructan-based, and Pirkle-type CSPs. Other types of CSPs, such as polymer- and cyclodextrin‑based, have not been found in recent publications. In this field of application, 3- and 5-μm fully porous particles (FPP) are the most common particles sizes for cellulose- and amylose-based columns. Smaller fully and superficially porous particles (SPP) are less common, but have proved to be successful in combination with macrocyclic glycopeptide- and cyclofructan-based stationary phases (6–8).

In the pharmaceutical industry, high‑throughput approaches are required during purity assessment tests. Due to the unique features of supercritical fluids, higher flow rates can be applied in SFC, which allow for high-throughput analysis. Barhate 

 showed that sub-minute separations are achievable with SFC after the selected drugs undergo an extensive column screening, followed by a method optimization when necessary (6), as illustrated in Figure 1. The overall goal of the study was to determine the feasibility of ultra-fast chromatographic chiral separations using improved CSPs, instrumentation, and particle technology. Nováková and Douša developed a new rapid and general screening and optimization approach for enantioselective SFC that is based on the enantioseparation success rates of different parameter settings (9). Rapid separations are helpful for the implementation of new high-throughput strategies, such as the so-called 

multiple injections in a single experimental run

 (MISER) to reduce analysis time and simplify data analysis (10). This approach performs rapid-fire high-throughput injections of multiple samples, resulting in multiple sub-minute (enantioselective) separations within a single chromatographic run. Figure 2 presents a flow injection analysis-like chromatogram of benzoin enantiomers (10).

 demonstrated the enantioselective analysis of various 1,4-dihydropyridines in a pharmaceutical formulation using chiral SFC and immobilized polysaccharide-based CSPs (11). Using a miniaturized sample preparation approach, that is, a two‑phase hollow fibre-based liquid‑phase microextraction (2p-HF‑LPME), the concentrations of nimodipine enantiomers in tablets were determined, with recoveries up to 99.8%. Pandya 

 showed the successful separation of four stereoisomers of luliconazole in a cream formulation (12). In addition, they determined the relation between elution order and binding energies, enabling a better understanding of the different interactions involved during the chiral recognition of luliconazole stereoisomers. The main reason for choosing chiral SFC over chiral LC was the speed of analysis, with the added advantage of minimizing toxic organic waste generation.

Traditional Chinese drugs (TCD) also contain pharmaceutically active compounds with one or multiple chiral centres. An example is the dried roots of 

, which is traditionally used against fevers, and contains the substance goitrin. (R)-goitrin is considered the therapeutic form, while its enantiomeric pair causes adverse effects on the thyroid gland (13). Wang 

developed an SFC-photo diode array-MS (SFC–PDA–MS) approach to enable the analysis of the enantiomeric forms of goitrin in both dried root extracts and commercially available pharmaceutical formulations.
The proposed method, based on a Pirkle-type CSP, led to the successful separation from plant matrix interferences, while it simultaneously provided enantiomeric separation. The developed method was eight times faster than the traditional normal-phase LC–UV analysis but with lower sensitivity. Nie 

 later developed an analytical and preparative method for the analysis of the same drug, using an immobilized cellulose-based CSP that led to improved chromatographic efficiency and analysis time. The comparison of both methods is shown in Figure 3 (14).

Once a drug is administered, chiral inversions may change the spatial configuration of a drug molecule and its metabolites (15,16). These in vivo by‑products and intermediates should thus be monitored and individually evaluated for their pharmacologic activities. Biofluids, such as plasma and serum, are complex matrices, with thousands of endogenous analytes that can affect the analytical performance. Moreover, a parent drug and its potential metabolites are typically present at low concentration levels. In this context, SFC–MS is often required to achieve sufficient selectivity and sensitivity for compound identification and quantification. Table 2 provides an overview of the clinical applications reported for the analysis of drugs and drug metabolites since 2015 (4,5).

 showed the applicability of SFC–MS/MS to investigate the potential in vivo chiral inversion of three different novel drugs in various mammal plasmas (16). While the drugs GNE-A and GNE-B showed no inversion a few hours after administration, inversion occurred with GNE-C up to 25%. However, as is shown in Figure 4, inversion was only observed in mouse plasma. For that reason, chiral inversions do not only require a specific chiral centre, they also depend on the biological environment in which the chiral drug is located. A study by Licea-Perez 

demonstrated the chiral inversion of the novel (S)-GSK-B drug to (R)-GSK-B (17). While the method was successful for the analysis of standards, no inversion was detected in rat plasma after administration.

 employed SFC–MS/MS to study the pharmacokinetics of the chiral drug rabeprazole (18). After administration of racemic rabeprazole to beagle dogs, repetitive chiral analysis of their serum was performed, showing a change in the enantiomeric ratio over time. This shift indicated that rabeprazole exhibited stereoselective pharmacokinetics properties. One of these enantiomers was then more effective than the other.

Drug metabolites are also relevant, as they can be either chiral or achiral. After detecting these minor by-products in vivo, the potential presence of their stereoisomers must be monitored and their pharmacological activities assessed. Another study by the group of Licea-Perez investigated the drug metabolism of the drug GSK1278863, developed for the treatment of anaemia correlated to chronic kidney disease (19). An SFC–MS/MS method was developed for the detection of six predominant metabolites formed by cytochrome P450 enzymes, which are responsible for the formation of 14 stereoisomers. Figure 5 shows the stepwise analyzing process for the full (enantiomeric) assessment of this investigative drug (19).

Online supercritical fluid extraction and chiral SFC–MS (SFE–SFC–MS) analysis have been performed by Hofstetter 

 for the extraction and quantification of ketamine enantiomers and their chiral metabolites in a dried urine sample (20). It proved to be the most efficient approach for ketamine analysis and was the first SFE–SFC–MS method to be validated according to the international EMA regulatory guidelines. Automated SFE was a more time-efficient approach to extract the relevant ketamine substances than via the previously described liquid–liquid extraction (LLE) method; it also reduced the necessary amount of biological matrix (20 μL) required for enantioselective quantification (21). The use of SFE–SFC demonstrated promising possibilities and represents an interesting approach in the pharmaceutical industry.

Chiral SFC has been used in doping research to determine whether athletes have been exposed to a doping agent by drug administration or by consumption of specific foods. An example was presented by Parr 

 where SFC–MS/MS was used to trace the origin of the doping agent clenbuterol by determining the enantiomeric ratio (22). Previous studies showed that the concentration of clenbuterol enantiomers in meat changed due to (different) pharmacological activities in animals, while no changes were observed in human urine within 18 h of administration. This difference in enantiomeric ratio can therefore provide information about the origin of the doping agent and ensure that athletes can be fairly judged.

Enantioselective SFC has been increasingly used in forensic investigations for a variety of illicit and licit drug-related purposes (3). Novel psychoactive substances (NPS) may be one of the most important motivators for chiral studies of these new derivatives (23). Due to their novelty, little is known about the pharmacological activities of NPS and their enantiomeric counterparts. Enantioselective separations are therefore of great importance to help identify NPS and evaluate their effects on the human body. Additionally, chiral assessments can provide information about the time of consumption by monitoring the enantiomeric ratio in human serum, as demonstrated by Losacker 

 using LC–MS/MS (24). However, this latter application has not yet been described for chiral SFC. Table 3 lists an overview of various forensic toxicology applications from the past five years using chiral SFC (4).

, various NPS classes (pyrovalerone, benzofuran, phenidine, and phenidate derivatives) were analyzed by SFC and LC using a core–shell vancomycin‑based CSP (23). The vancomycin-based chiral selector showed high enantioselective properties for both approaches, resulting in fast and highly efficient enantiomeric separations. This study showed the complementarity between SFC and LC for chiral analysis. Overall, 88% of the NPS enantiomers were separated by SFC, while only 69% of NPS enantiomers were separated with LC. Both approaches were potentially able to separate most of the known NPS enantiomers, as well as those yet to be discovered. Additionally, the vancomycin-based methods can be used for the analysis of seized samples and perform simultaneous multiple enantiomeric separations—beneficial for full purity profiling.

Some listed drugs are not only used for recreational purposes but are also administered for medical reasons. It is therefore of great importance to be able to distinguish between these two scenarios of administration for lawful conviction. Dextromethorphan (

-enantiomer), for example, is an antitussive drug that can be purchased without a prescription. Levomethorphan (

-enantiomer), however, is a strong narcotic analgesic and is registered as a controlled substances in many countries (25). Li 

 developed a direct enantioselective SFC–MS method to separate these enantiomers within 3 min using an amylose-based CSP (26). A similar study was performed by Hegstad 

, in which an SFC–MS/MS method was developed to separate and quantify (

)-amphetamines in urine, to distinguish between medical (legal) and recreational (illegal) intake (27). In most cases, the pure 

-enantiomer of amphetamine or its prodrug was prescribed as the medical drug, while illicit amphetamine mainly occured as a racemic mixture. The developed SFC approach has recently been extended by Havnen 

 to analyze serum and blood samples (28).

 demonstrated in successive studies the potential of using those particular enantiomeric ratios to trace back the origin of seized methamphetamine by identifying their precursors and synthetic route (29,30,31). Together with various ephedrine derivatives (EP derivatives) and phenyl-2-propanone (P2P) as starting material, and different optional reaction pathways, there are many ways to produce methamphetamine (MA; crystal meth). Segawa 

 demonstrated a simultaneous chiral analysis of methamphetamine and its precursors using a polysaccharide‑based CSP analyzed with SFC–MS/MS (30). Such an approach allows for a direct and fast determination of a potential synthetic route. Additionally, each of these synthetic routes leads to their own typical chiral MA impurities in specific enantiomer ratios, which makes it possible to trace back the original precursor and method used. This information can be helpful by linking the seized drugs to potential clandestine production laboratories.

 extended this chiral SFC profiling approach to the analysis of seized MA by including the analysis of EP stereoisomers (31). It has recently been reported that ephedrine and pseudoephedrine are by-products from the P2P synthesis. Both forms of ephedrine are therefore ultimately present in the phenyl-2-propnanone-based MA samples and can be used for sample identification.

Pharmacological active compounds (PACs) are increasingly seen as major pollutants within ecological systems. However, despite the known concerns of these drug stereoisomers, research on their ecotoxicological effect is still limited (32). One of the reasons for this shortfall is the lack of knowledge on the potency of different enantiomeric forms, as well as sensitive and efficient methods. Besides in vivo inversions and metabolism after administration, drug substances may undergo further modifications initiated by wastewater treatments and biological processes (33). These reactions are usually enantioselective and therefore enrich or deplete one enantiomeric form over the other, which may increase the environmental impact. Table 4 lists the various applications in which chiral SFC has been implemented into environmental studies (4,5).

Sensitive chiral systems are essential to detect even the most diluted substances as well as their enantiomeric opposites to fully profile the drug content in water. Rice 

developed an SFC–MS/MS method for multiresidue analysis of both chiral and achiral PACs in waste- and natural waters (32). Over 80 PACs were successfully separated within 10 min of analysis, including enantiomeric separations using a polysaccharide-based CSP. Additional chiral analysis proved the occurrence of configurational modifications, as the uneven enantiomeric ratios in influent, effluent, and natural water differ from each other. However, as these water samples were collected at one specific location and time point, no firm conclusions could be drawn.

Racemic drugs are most likely affected by in vivo and/or natural microbiological reactions. Earlier studies by Svan 

 using (UHP)SFC–MS/MS and polysaccharide‑based CSPs showed similar activities in enantiomeric conversions of various PACs in wastewater and wetland microcosm samples (34,35). Figure 6 shows the influence of different wetland sediment environments on the enantiomeric fraction of metoprolol, atenolol, and propranolol (34). No significant changes occurred at 1 ppb, but atenolol showed a slight increase at 100 ppb. This indicates an enantioselective enzymatic process that may participate in its breakdown.

SFC proved to be a worthy alternative for efficient analysis of environmental samples, by allowing for enantiomer‑specific evaluations on the ecological impact of drugs. Analysis of influent and effluent water can also provide additional information about the use of drugs within a specific area, including whether it is legal (prescribed) and/or illegal (recreational) consumption. Finally, this information may be used in pharmaceutical studies to complement in vivo metabolomics-based approaches or within forensic investigations for determining the origin of the drugs.

The technological developments in (chiral) SFC have made this a competitive technique for enantioselective separations with respect to conventional LC. Advantages include the achievement of efficient separations within a reduced analysis time and the replacement of toxic solvents (for example, from reversed-phase LC) with CO2. These have been covered in more details in part 1 of this review (2).

In chiral analysis, method optimization remains a complex and timely process. Notably, the selection of the adequate CSP column is a time-consuming but essential screening step, since each chiral selector interacts differently with a specific chiral molecule. Hundreds of CSPs have been developed, without one specific phase that can be labelled as universal. Such a CSP would be highly beneficial, as this would significantly simplify the method development. Future studies focusing on the development of universal enantioselective column chemistries are therefore needed to ensure optimal chiral distinctions for as many different stereoisomers as possible. In parallel, innovative workflows enabling the screening of a large diversity of phases are also beneficial. These workflows can be specialized for single column systems (36,37,38), tandem column systems (39,40), or stereoisomers with multiple chiral centres (MCC) (41). De Klerck 

proposed a generic screening strategy when investigating the effect of different CSPs in combination with varying mobile-phase compositions, and used principle component analysis (PCA) to confirm selectivity differences between the screened SFC systems (36). Hegade 

 proposed a new effective screening method called 

stationary-phase optimized selectivity supercritical fluid chromatography 

for the prediction of elution profiles of tandem column systems (40). This approach is based on the combined interaction models from the individual columns used. Lin 

 developed an effective screening strategy for stereoisomers with single and multiple chiral centres, answering several key questions regarding which parameters to use for optimal MCC compound coverage (41).

The potential of chiral SFC application outside of the pharmaceutical industry has been minimally explored so far. A few publications have demonstrated promising applications and strategies but only for a limited number of drugs. Further implementation of chiral SFC into clinical, forensic, and environmental drug‑related studies are therefore encouraged to foster the acceptance of chiral SFC in a broad spectrum of real-life cases. Specifically, the determination of the ecotoxicological effects of drugs after consumption deserves more attention and should be more predominant within drug development processes. In addition, successive studies can be of added value to determine how the obtained data can be used in a larger perspective. Further implementation and new developments are expected to be promising based on the cost-saving and green advantages, applications, and strategies mentioned in this review.

SFC mechanisms exhibit high orthogonality compared to LC-based separation techniques. With the development of special interfaces, the rise of multidimensional applications with SFC included as one of the two dimensions is, therefore, no surprise. Various setups for chiral separations have been proposed, demonstrating a highly selective and efficient achiral impurity assessment in the first dimension and chiral distinction in the second. Despite the good enantiomeric resolution acquired, sensitivity in 2D applications remains a challenge because it is important to detect trace-level impurities. Moreover, hardware and solvent incompatibility may form a limitation in this field of application. Further studies and instrumental developments are required to tackle these drawbacks and would be of great value to fully assess (enantiomeric) purity or activity within a single run. Still, the complexity and input required to fully optimize such a system for integrated achiral and chiral impurity assessment is intensive and time-consuming. It is therefore recommended to first apply simpler optimization approaches to resolve difficult enantiomers rather than directly developing a 2D-system. Such approaches include changing the CSPs, tandem column setups, or selecting a different detector. Nevertheless, further studies in 2D chiral applications are still important because this approach may be required in complex cases.

Nowadays, chiral SFC is not only recognized for its success on a preparative scale but has also been demonstrated to be a worthy asset for analytical purposes. SFC provides high-efficient and complementary chiral separations, allows high-throughput analysis, is eco-friendlier and safer than traditional chiral normal-phase LC, and is cost-efficient. Despite these advantages, there are still some challenging hurdles to overcome. Bottlenecks are undefined chiral recognition mechanisms, lack of highly universal CSPs, time-consuming screening approaches, relatively low maximum system back pressure, and minimally explored instrumental and applicational strategies. If the current aforementioned bottlenecks are studied and optimized, chiral SFC certainly has a thriving future in enantiomer assessments in various drug-related fields, as highlighted by recently reported applications in the fields of drug development, clinical research, forensic toxicology, and environmental studies.

G. Roskam, B. van de Velde, A. Gargano, and I. Kohler, 

M. Gumustas, S.A. Ozkan, and B. Chankvetadze, 

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P.A. Pandya, P.A. Shah, and P.S. Shrivastav, 

M. Goel, E. Larson, C.J. Venkatramani, and M.A. Al-Sayah,

L. Chen, B. Dean, H. La, Y. Chen, and X. Liang, 

H. Licea Perez, D. Knecht, and C.A. Evans, 

R. Hofstetter, G.M. Fassauer, and A. Link, 

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S. Hegstad, H. Havnen, A. Helland, O. Spigset, and J. Frost, 

H. Havnen, M. Hansen, O. Spigset, and S. Hegstad,

J. Rice, A. Lubben, and B. Kasprzyk-Hordern, 

D. Camacho-Muñoz, B. Kasprzyk-Hordern, and K.V. Thomas, 

K. De Klerck, C. Tistaert, D. Mangelings, and Y. Vander Heyden, 

K. De Klerck, Y. Vander Heyden, and D. Mangelings,

T.A. Berger, B.K. Berger, and K. Fogleman, 

R. Geryk, K. Kalíková, M.G. Schmid, and E. Tesařová, 

J. Storch, K. Kalíková, E. Tesařová, V. Maier, and J. Vacek,

X. Bu, E.L. Regalado, J. Cuff, W. Schafer, and X. Gong,

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M. Iguiniz, E. Corbel, N. Roques, and S. Heinisch, 

Articles

Peer Reviewed

In the second part of this review article, the recent progress in SFC for enantiomeric separations is evaluated. Several applications reported on the enantioselective separation of drugs and pharmaceutical compounds using chiral SFC are discussed, including pharmaceutical applications, clinical research, forensic toxicology, and environmental sciences.

Supercritical Fluid Chromatography for Chiral Analysis, Part 2: Applications

Choosing a liquid chromatography (LC) column for a particular application can be a surprisingly challenging task. On one hand, column manufacturers give us many options to choose from, including particle types, pore sizes, particle sizes, and different lengths and diameters. On the other hand, we usually don’t have time to experimentally evaluate many combinations of these parameters, and sometimes we end up picking something similar to the columns that are already in the drawer. The “kinetic plot” is a powerful graphical tool that can help leverage the best available theory to help us understand how different combinations of parameters (that is, particle size and length) will perform in terms of the time needed to get to a particular column efficiency (and thus resolution), and therefore make well-informed decisions when choosing columns.

In the last two instalments of “LC Troubleshooting”, we reviewed the basic idea of a “kinetic plot” (1) and how to make the plots from experimental data or data from the literature (2). Ultimately, this graphical tool can be used to make informed decisions when choosing columns and to understand why a column might not be delivering expected performance improvements. This month, we conclude this series of articles by discussing the so-called “Knox-Saleem limit” (KSL), application of kinetic plots to gradient elution conditions, and the impact of extracolumn dispersion on kinetic plots. Finally, we introduce a web-based application that pulls together all of the theory discussed in these instalments into a convenient and flexible web‑based calculator that allows you to explore the impact of many variables on the kinetic plot on your own.

In last month’s instalment, we began discussing the effect of particle size on kinetic plots by showing the kinetic performance limit (KPL) curves for different particle sizes (Figure 1[a]). Interestingly, these curves cross in the kinetic plot, which means that at any given combination of 

, there is one particle size that provides superior performance compared to the others. In other words, there is no single particle size that is superior to all others over the entire range of analysis times of practical interest. Whereas the smallest particles (1.7 µm) show the best kinetic performance at short analysis times, the larger particles (5 µm) are the better choice to obtain high efficiencies at long analysis times, which is a direct result of the improved performance at higher flow rates for smaller particles (fast analysis). However, the small particles also lead to large pressure drops that limit their use to relatively short columns (lower efficiency).

In Figure 1(a), we see that each of the KPL curves touches an oblique asymptote (dashed lines) below which one cannot work regardless of the choice of column length, particle size, and velocity because the pressure drop will exceed the chosen pressure limit. This oblique asymptote is the KSL and in fact touches the KPLs for different particle sizes at their respective optimal mobile phase velocities (that is, 

) (3). The point where the KPL and KSL curves touch represents the optimal choice of not only mobile phase velocity and column length but also of the particle size for each combination of 

. For the particle sizes represented in Figure 1, we see that the KPL curves come very close to the KSL, which indicates that at least one of these particles is close to optimal for plate numbers in the range of 10,000 < 

 < 200,000. When there is a gap in the available particles sizes (for example, jumping from 1.7 to 3.5 µm), we see a gap between the points at which the two KPL curves cross with the KSL. This occurrence indicates a gap between the truly optimal performance that is possible for a given combination of 

, and what can actually be realized with the available particle sizes. Fortunately, these differences are rather small, as has been discussed in detail by Matula and Carr in the literature (4).

The KSL can be calculated using equation 1 if the dynamic viscosity of the mobile phase (η), the minimum reduced plate height (

) for a certain stationary phase support are known using (2,3,5):

This relationship makes clear that the kinetic performance can be improved by increasing the maximum operating pressure (Δ

; that is, ultrahigh-pressure liquid chromatography [UHPLC] vs. high performance liquid chromatography [HPLC]), decreasing the mobile phase viscosity (for example, through the use of high temperatures in LC, or low viscosity eluents in supercritical fluid chromatography [SFC]), reducing the flow resistance (for example, by using monolithic or chip-based columns), or decreasing the minimum reduced plate height (for example, with superficially porous particles, chip-based, or 3D-printed columns) (6). A change in any of these parameters will shift the KSL (and also the KPL curves) to the right, allowing for both faster and more efficient separations. When all other parameters are fixed, doubling Δ

 by a factor of two. In other words, doubling the available pressure allows the same efficiency to be realized in half the time, which is illustrated in Figure 1(b) where the effect of the operating pressure on the KPL curve for the 1.7 µm particles is shown (7). The curve shifts to the bottom right of the kinetic plot, showing how even faster analyses and higher efficiencies can be obtained when operating at this higher maximum pressure. In fact, when comparing the use of 1.7 µm particles at 1000 bar with 3.5 and 5 µm particles used at 400 bar, the smaller 1.7 µm particles outperform the 3.5 µm particles in the part of the efficiency analysis time range where the latter outperforms the 5 µm particles at 400 bar. The 1.7 µm particles at 1000 bar even outperform the 5 µm particles up to approximately 

 ~100,000. Of course, this comparison changes if the 3.5 and 5 µm particles can also be used at 1000 bar. Similarly to the KPL curve, the KSL also shifts with an increase in maximum pressure, as expected from equation 1.

Application of the Kinetic Plot Concept to Gradient Elution Conditions

For fundamental comparisons of the separation performance of different column types, it is most practical to use isocratic elution conditions, which is why our discussion of kinetic plots has so far focused on the kinetic plots with 

 as the axes. In practice, however, most applications use mobile phase composition gradients to optimize separation time and resolution. Thus, it is desirable to apply the kinetic plot concept to the gradient elution condition as well, which can be done by replacing the plate number with the peak capacity (

) as the measure of separation performance (5,8). When making experimental measurements of retention time and peak width under gradient elution conditions for the purpose of making kinetic plots from experimental data, several details are important to keep in mind. These are mentioned briefly here. Readers interested in learning more about them are referred to the literature for detailed protocols (9).

Gradient time should be scaled inversely proportional to the flow rate so that the gradient slope remains constant (10,11).

If the mobile phase composition is held constant at the beginning of the separation, or at any other point in the elution program, these so-called 

 should also be scaled with the inverse of the flow rate.

If columns with the same stationary phase chemistry from the same vendor are compared, there is usually little to no difference in selectivity and the same gradient range (initial and final composition) can be used. However, when comparing columns from different vendors, differences in retention may be observed, and it is advisable to tune the initial and final composition of the gradient in such a way that the first and last eluted compounds have similar retention factors (9,11).

As previously mentioned, in the case of gradient elution, the peak capacity (

) is usually the preferred measure of separation performance rather than the column plate count (

). Calculation of the column dead time and retention time at the kinetic performance limit (that is, 

) is similar in isocratic and gradient elution, however calculation of the peak capacity at the KPL is slightly different, as shown in equations 2 and 3 (9,10,12,13):

The square root dependence in equation 3 is the direct result of the square root dependence of the peak capacity on the column plate number (10). As a result, increasing the column length by a factor of four will only increase the peak capacity by a factor of two. Please note that also in this case the value for Δ

 should include the extracolumn pressure drop as discussed in the next section.

Effects of Extracolumn Dispersion on Kinetic Plots

So far in this series, we have not discussed the impact of extracolumn dispersion (ECD) on kinetic plots, which is mathematically convenient. However, peak dispersion outside of the column is often too large to ignore. We discussed the details associated with dispersion in different parts of the LC system in a prior multipart series of articles in this magazine (14–17) and elsewhere (18), and readers interested in these details are referred there. Here, we focus on adjustments that must be made to the kinetic plot calculations to account for both the dispersion that occurs in the LC system outside of the column, and the pressure drop that occurs in different parts of the system.

Corrections to the kinetic plot calculations to account for extracolumn effects can be made using values for the extracolumn dispersion and pressure drop obtained from experiments, or some means of estimation. When it comes to experimental measurements, the column is replaced by a zero dead volume union in order to obtain the extracolumn time (

) at different flow rates. It is important to understand that extrapolation of the plate number from a FL curve to the KPL using λ = Δ

 (as discussed in Part 2 of this series) should only be done using plate numbers that have been corrected for ECD. Then, after the extrapolation, the extracolumn variance is added back to the peak variance contributed by the column to give an effective plate number (

) as shown in equation 4. Similarly, the column dead time must be corrected to account for the time the analyte spends travelling from the injector to detector, but outside of the column, as shown in equation 5:

In addition to the effect of the LC system on dispersion of peaks, some of the available operating pressure is also lost because of pressure drops along the connecting tubes, especially when narrow diameter tubes are used. To account for this, the value of Δ

 used in calculating the kinetic curves should be reduced by the value of the extracolumn pressure drop (Δ

) at the corresponding flow rate, as shown in equation 6:

Pulling It All Together—A Web‑Based Application for You

Although no single mathematical step in calculating the kinetic curves is particularly difficult, there are many details to keep track of, and building a calculator correctly from scratch takes some time. Thus, we have built a freely available web-based calculator (www.multidlc.org/kinetic_plot_tool) that incorporates all of the theory discussed in this series of articles, including consideration of extracolumn effects discussed in the previous section. Here, we briefly demonstrate use of the tool by way of an example that shows how it can be used to explore the effects of different variables on the curves, and perhaps develop hypotheses for troubleshooting situations where column performance does not live up to one’s expectations.

Figures 2 and 3 show screenshots of the inputs to the tool. Up to three different conditions can be compared simultaneously. Pre-set configurations for zero, low (~1–2 µL2), and normal (~10–15 µL2) levels of extracolumn dispersion enable quick configuration of the extracolumn inputs; however, each of the system parameters (that is, injector, tubing, and detector) are fully adjustable as well.

Figure 4 shows screenshots of the kinetic plots produced by the tool for two different cases (A and B). In both cases the comparison is between columns packed with fully porous 1.7 µm particles and columns packed with superficially porous 2.7 µm particles. In case A, the tool is configured using the pre-set parameters for a low dispersion system (~1–2 µL2) for both the FPP and SPP columns. Here, we see that the 1.7 µm FPP columns outperform the 2.7 µm SPP ones at the KPL over the range of 5000 < 

 < 30,000, though the difference is small (

 = 0.31 min for 15,000 plates). At approximately 

 = 30,000 plates, the curves cross over and the SPP columns become superior for higher efficiencies as a result of their higher permeability.

However, when the tool is reconfigured using the preset parameters for a normal dispersion system (~10–15 µL2), we get the curves shown in Figure 4(b), where the SPP columns are superior to the FPP ones at the KPL over the entire range of efficiencies shown. On one hand, the superiority of SPP columns is not surprising: manufacturers of sub-2-µm columns have been working to educate users for years about the importance of using these columns in low dispersion systems to maximize their performance potential. On the other hand, this comparison shows the utility of the kinetic plot tool, both for making informed choices about column selection and troubleshooting situations where a column in use does not live up to user expectations.

In this instalment of “LC Troubleshooting”, we have continued our discussion of kinetic plots and their utility when selecting column technologies and formats, and troubleshooting columns that appear to not live up to our expectations. The KSL quantifies the best achievable performance (as measured by plate number) in a given analysis time when the particle size is allowed to vary. Kinetic plots can also be used to compare technologies under gradient elution conditions, and when the effects of extracolumn dispersion are accounted for. Finally, we have introduced a freely available web‑based kinetic plot tool that leverages all of the theory discussed in this series and enables comparison of up to three different sets of conditions simultaneously. This tool is useful for quickly comparing different column technologies and LC system configurations, and developing troubleshooting hypotheses when things don’t seem to be quite right. It is important to note that all calculations in this series have been done with diffusion coefficients typical of small molecules. When working with large molecules their diffusion coefficients will be very different, and thus the kinetic plots will be very different as well.

G. Desmet, D. Cabooter, and K. Broeckhoven, 

Y. Vanderheyden, D. Cabooter, G. Desmet, and K. Broeckhoven, 

X. Wang, D.R. Stoll, P.W. Carr, and P.J. Schoenmakers, 

K. Broeckhoven, D. Cabooter, S. Eeltink, and G. Desmet, 

K. Broeckhoven, D. Cabooter, F. Lynen, P. Sandra, and G. Desmet, 

K. Broeckhoven, D. Cabooter, and G. Desmet, 

T.J. Causon, K. Broeckhoven, E.F. Hilder, R.A. Shellie, G. Desmet, and S. Eeltink, 

D.R. Stoll, T.J. Lauer, and K. Broeckhoven, 

 is Associate Professor at the Vrije Universiteit Brussel (VUB), in Brussels, Belgium.

 is currently a student and a researcher in the Stoll laboratory at Gustavus Adolphus College in St. Peter, Minnesota, USA.

 is the editor of “LC Troubleshooting”. Stoll is a professor and the co-chair of chemistry at Gustavus Adolphus College in St. Peter, Minnesota. Direct correspondence to: amatheson@mjhlifesciences.com

LC Troubleshooting

The impact of extracolumn dispersion on kinetic plot curves is investigated. A web-based calculator that allows users to make their own kinetic plots with examples of how the tool can be used to troubleshoot underperforming columns and support column selection is discussed.

But Why Doesn’t It Get Better? Kinetic Plots for Liquid Chromatography, Part 3: Pulling It All Together

I am pleased to present our annual review of new products in gas chromatography (GC), introduced between spring 2021 and spring 2022. With the Covid-19 pandemic still impacting travel and conferences, the 72nd meeting of the Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy (Pittcon) from 8–12 March 2022, originally scheduled to take place in Atlanta, Georgia, USA, was cancelled at the last minute. Although many of the technical presentations were conducted virtually, there was not sufficient time to re-tool the exposition, so this review was conducted virtually for the second year in a row.

Pittcon 2023 will be held from 18–22 March 2023, in Philadelphia, Pennsylvania, USA. Although this year we are transitioning out from the pandemic more slowly than was anticipated, I challenge everyone to attend a professional conference over the next year. Also, everyone consider participating in a local or regional chromatography discussion group or local section of the American Chemical Society (ACS) meeting. In the remainder of 2022, I will not be travelling far, but I will be dipping my toes back into conference attendance. I will be attending both the Middle Atlantic Regional ACS meeting in Ewing, New Jersey (NJ), and the ACS Green Chemistry Institute Meeting in Reston, Virginia, both in June 2022, as well as the Eastern Analytical Symposium in Princeton, NJ, in November 2022. I have used the increase of virtual conferences to attend additional meetings that I would not have attended otherwise because of the travel costs, but I will return to attending my usual set of in-person meetings as they come back. Two years of being stuck in a global pandemic were extremely difficult for conference organizers and for the many vendors, contractors, and economies that the conferences support. They still need your help, even more than last year. Conference and meeting attendance is still the best way to improve skills, learn about new techniques, train, and educate yourself.

In the specific space of gas chromatography (GC), I highly recommend the virtual 19th International GC×GC symposium, originally scheduled for Canmore, Alberta, Canada, from 29 May to 2 June 2022. This meeting will include many of the best minds in comprehensive two-dimensional GC (GC×GC) and GC, and it is of special interest to anyone who has heard about GC×GC and wants to learn more about it. The list of speakers is an international all-star list of top chromatographers. I also highly recommend 

s GC ChromTalks, also virtual, on 24 May 2022. We have five speakers, all of whom are all-stars in GC, and a live question and answer virtual session will serve as an opportunity for everyone to learn more about GC and to get their questions answered.

There was no virtual exposition at the virtual Pittcon this year. The virtual technical programme, which was much more limited, included key invited and award sessions and ran throughout the month of March. It was presented at no charge, although registration was required to obtain links to the talks. GC continues to have a strong presence on the conference circuit and in the literature. Topics such as cannabis analysis, biofuels, food and beverages, forensics, pharmaceuticals, and general applications of both GC and GC×GC are seen in a robust publication space. GC itself is trending towards being less the driver of research than its application to scientific problems. The most effective online search for GC today probably begins with phrases such as “GC of ____”, with your analyte or sample of interest filling in the blank.

The information presented in this article is based on vendors’ responses to questionnaires and additional information from press releases, websites, and product literature, not on the actual use or experience of the author. Every effort has been made to collect accurate information, but because of the preliminary nature of some of the material, 

 cannot be responsible for errors or omissions. This column cannot be considered a complete record of all new GC products introduced in the past year because not all vendors responded to the questionnaire, and not all the submitted information is necessarily included here because of the limited available space and the editors’ judgement as to its suitability. Table 1 provides a listing of the vendors highlighted in this review, some of whom are lesser known in the areas they are listed, showcasing new products this year, or both. For a more complete picture of the GC space today, I encourage you to review the three previous years’ reviews (1–3).

In new instruments, trends seen over the past few years towards smaller, more automated systems, more specialized systems, and spectrometric detectors continue this year. Table 2 shows a list of new complete instruments introduced over the past year. All these systems are designed with optimizing and simplifying workflows, operation, and maintenance in mind. One concern is that systems are becoming so automated and convenient to use that training and education may be viewed as less necessary, which is a seemingly reasonable view until something goes awry.

Stationary phases continue to be updated by most of the vendors, with nearly all making incremental improvements or showing new applications in their online application note libraries. The one new stationary phase that appeared in this year’s survey was a packed column phase, indicating the continued need for high retentivity columns for light gas separations. This phase is highlighted in Table 3. The incremental trend in capillary column stationary phase development for specific specialized problems continues. The 2021 review included two phases for fatty acid methyl esters and dioxins. Users are encouraged to contact and keep up with your column vendor; new phases and improvements are happening continuously.

In 2021–2022, developments in new accessories and consumables continue to trend towards simplifying analysis and making chromatographers’ work easier. Manufacturers of accessories and consumables are also developing ways to improve inertness in the sample flow path. Accessories and consumables for sample preparation are not covered broadly here. For more information on sample preparation, see the specific sample preparation article by Doug Raynie in the next issue of 

. As with the GC reviews, it is worthwhile to review the past two years as well for a complete picture of sample preparation products (4,5). Table 4 provides a listing of products released in the past year that illustrate this trend. Many of the accessories are instrumental improvements in detectors and sampling devices.

Our emergence from the pandemic provides more opportunities to continue education and training. Besides numerous short courses associated with Pittcon and other major conferences, many additional training and educational resources are available for 2022. The pandemic has resulted in much growth in online training and seminar offerings by vendors and training organizations, so check with your vendor. Opportunities for in-person short courses, seminars, and training are beginning to start up again and are offered by most major instrument vendors and through many conferences and organizations, including ACS, the Eastern Analytical Symposium (Princeton, NJ, November 2022), and local and regional chromatography discussion groups. 

’s online training system, CHROMacademy, launched a completely revamped online platform in 2020 and is again hosting ChromTalks, a virtual symposium in May 2022.

As GC nears its 70th birthday, development and innovation are ongoing and include all areas: sampling and supplies, new instruments, columns, detectors, data systems, and educational opportunities. I look forward to more innovation and advancements in the 2020s, and I hope to see many of you at EAS 2022 in my home state of New Jersey or at Pittcon 2023 in Philadelphia.

 is Founding Endowed Professor in the Department of Chemistry and Biochemistry at Seton Hall University, and an Adjunct Professor of Medical Science. During his 30 years as a chromatographer, he has published more than 70 refereed articles and book chapters and has given more than 200 presentations and short courses. He is interested in the fundamentals and applications of separation science, especially gas chromatography, sampling, and sample preparation for chemical analysis. His research group is very active, with ongoing projects using GC, GCÐMS, two-dimensional GC, and extraction methods including headspace, liquidÐliquid extraction, and solid-phase microextraction. Direct correspondence to: amatheson@mjhlifesciences.com

GC Connections

“GC Connections” presents the column’s annual review of new developments in the field of gas chromatography made available in 2021–2022.

New GC Products for 2021–2022

This instalment describes newly introduced high performance liquid chromatography (HPLC), mass spectrometry (MS), chromatography data systems (CDS), and related products in 2021–2022 and prior years. It summarizes their unique features and significant user benefits.

The 74th Pittcon was supposed to be held at Georgia World Congress Center in Atlanta, USA, from 5–9 March 2022. Unfortunately, the global conference was cancelled in mid-January due to the continuing surge of the omicron variant in America. The abrupt cancellation resulted in a limited virtual technical programme without any exposition or short courses. Therefore, the product information collected here is based solely on manufacturers’ websites, returns from the annual 

 survey, and direct communication from my personal contacts.

Current Product Trends of HPLC and MS Instruments

The current high performance liquid chromatography (HPLC) and mass spectrometry (MS) instrument portfolios utilize mature technologies that have benefitted from decades of continuous product improvements.
The advent of ultrahigh-pressure liquid chromatography (UHPLC) and its first product commercialization in 2004 (1) had brought on a surge of instrumental redesigns and a tidal wave of new product offerings by the four leading manufacturers in recent years (Waters, Agilent, Shimadzu, and Thermo Fisher Scientific) (2). The MS instrument market is dominated by the same four big manufacturers, plus Sciex and Bruker (2).

While there were fewer new introductions or significant upgrades of HPLC instruments, manufacturers have added systems with intermediary pressures, dual‑injection, or multidimensional capability. Many expanded their product offerings in preparative purification, micro‑LC, bio-inert, and application‑specific systems in areas such as amino acid analysis, cannabis assays, two-dimensional liquid chromatography (2D-LC), method development, and clinical diagnostics (3–5).

Similar paths were followed for MS instrumentation, with trends towards more compact single quadrupole (SQ) or triple quadrupole (TQ) MS, ion mobility MS (IMS), direct sampling of solids and systems focused on specific applications such as multi-attribute biopharmaceutical analysis, clinical diagnostics, and biological imaging (2–5).

Table 1 lists new product introductions ordered alphabetically by the vendor’s name from 2021 to 2022, categorized as HPLC systems, modules, MS, chromatography data systems (CDS), and other software. The HPLC system category includes ion chromatography (IC) and supercritical fluid chromatography (SFC) instruments. Key innovative features and benefits of each product are briefly described later. Several products or upgrades introduced before 2021 are included here since they were not covered in previous instalments. The footnotes of Table 1 contain the definitions of common acronyms used later in the text.

The introduction of new UHPLC systems has slowed as manufacturers focused more on HPLC line extensions for higher productivity, ease of use, and specific applications such as 2D‑LC, biopharmaceutical multi-attribute methods (MAM), cannabis analysis, and clinical diagnostics (2–5). The followings are brief descriptions of those products with significant impacts. The reader is referred to manufacturers’ websites and product brochures for more details and specifications.

Agilent offers an extended family of bio-inert versions based on a nickel alloy MP-35N for the three Infinity II UHPLC systems (1290, 1260, and 1260 Prime Infinity II). Features available for these systems include Intelligent System Emulation Technology (ISET), Instrument Control Framework (ICF), and LC–MS or size-exclusion chromatography (SEC) capabilities.

An extensive family of HPLC purification systems based on 1220, 1260, or 1290 Infinity II modules ranging from analytical-scale to semi-preparative and preparative-scale with flow ranges up to 200 mL/min and software towards workflow automation. An extensive range of detection options is available (ultraviolet [UV,], mass spectrometry detection [MSD], evaporative light scattering detection [ELSD], fluorescence detection [FLD], and refractive index detection [RID]).

Agilent Application-Specific HPLC Systems: 

Agilent offers 21 application systems ranging from amino acid analysis, bio-inert applications, bio-inert SEC multi-detectors, gel permeation chromatography (GPC), supercritical fluid chromatography (SFC)/UHPLC hybrid, 2D-LC, 2D-LC (Bio), wide dynamic range impurity analyzer, high-throughput screening (HTS), method development and transfer, multimethods, and online solid-phase extraction (SPE) applications.

Agilent 1260 Infinity II Prime Online LC System:

 A process analytical technology (PAT) tool for automated process monitoring with customizable features such as online mix/dilute feed injections, high precision for 0.1–100 µL injection volumes, 600-bar system pressure, and enhanced software for in-process control (IPC).

 A compact LC–UV system with a 20-position autosampler, 10,000-psi binary gradient pumps, variable UV detector, and easy-to-use CDS software.

 Metrohm offers an extensive family of IC systems, including the 940 Vario Professional for multi-channel analysis, the 930 Compact IC Flex for single-channel routine analysis, and the Eco IC entry-level systems for water analysis.

PerkinElmer LC-300 HPLC and UHPLC Systems with Quaternary Pumps: 

PerkinElmer adds two new systems to its LC-300 HPLC product line with quaternary pumps rated at 10,000 or 18,000 psi.

 PATfix HPLC is designed for in‑process monitoring in biopharmaceutical development and production (gene therapies and vaccines). It is based on a bio-inert ceramic gradient pump with flow rates of up to 10 mL/min coupled with a UV or fluorescence detector. It uses customized monolithic columns for product monitoring or purification. The PATfix software offers a single database of chromatograms for multiple analytical systems with data visualization and report generation capabilities.

The BioPhase 8800 is a multi-capillary electrophoresis (CE) system for biopharmaceutical analysis that can run eight samples simultaneously, including modes of CE-sodium dodecyl sulfate (SDS) and capillary isoelectric focusing (CIEF).

Shine Qingdao Shenghan Chromatograph Technology CIC-D300

 This is a dual-channel IC with a smaller flow path, built-in eluent generator, and a new sampling system capable of analyzing cations and anions simultaneously with a pressure rating of 42 MPa. The improved suppressed conductivity detector delivers a 50% higher sensitivity than its predecessor. Figure 1 shows the sensitivity performance of this new IC in the analysis of common anions in electronic grade water at ppb levels.

 Two i-Series HPLC integrated systems based on the LC-2050 or LC-2060 with upper-pressure limits of 7000 psi or 10,000 psi are offered with UV/photo diode array (PDA) detection. Enhancements include a mobile phase monitor, flow pilot, intelligent peak deconvolution, and a simplified user interface. Bio‑inert options are available for high-salt or pH mobile phase operations.

Nexera XS inert is a bio-inert HPLC system for protein and nucleic acid applications sensitive to metallic surfaces. The system is constructed with anti-corrosive, non‑stainless steel alloys and is based on the new LC-40D XSi solvent delivery unit (up to four pumps can be configured) and a SIL-40C XSi autosampler. System specifications are: pressure rated at 105 MPa; flow range to 3 mL/min, and pH compatibility range of 1–14.

Shimadzu Nexera-i MT Method Transfer System:

 An HPLC system with dual flow lines simplifies the migration of HPLC methods to UHPLC conditions or vice versa. The system is equipped with Analytical Condition Transfer and Optimization (ACTO) software and the ability to select two delay volumes using a built-in 10-port valve for automated flow path switching.

Shimadzu LabSolutions Method Development System:


The method development system can be configured with modular Nexera or integrated i-Series HPLC/UHPLC systems with automated column/mobile phase screening capability based on the concepts of design of experiments (DoE), predictive simulation, and analytical quality by design (AQbD) optimization algorithms.

 Shimadzu offers two Nexera Prep systems: LC-20 AP prep purification (150 mL/min, 43 MPa) and LC-20AR semi-prep systems (20 mL/min 49 MPa) using a column hub (column switching), fraction collector (FRC-40 open bed test tubes), and LH-40 Prep Liquid handler (autosampler/collector).

 The ACCQPrep SFC is a compact system that simplifies complex separations and ensures success for users of all experience levels. It offers bulk collection from stacked injections and multi-sample, walk-up, open-bed collection in one unit. The unit has a PDA detector with a gradient pump of 50–300 mL/min flow rate for columns up to 3-cm internal diameter (i.d.).

An all-in-one low‑flow UHPLC for micro-, capillary-, and nano-LC. Specifications are: flow ranges from 1 nL/min to 100 µL/min without pump hardware changes; injection volumes of 0.01–100 µL; pressure up to 1500 bar.

Thermo Scientific Vanquish HPLC and UHPLC Portfolio: 

The Vanquish product portfolio consists of the Vanquish Core (700 bar, iso/bin/quat/dual), Vanquish Flex (bio1000 bar, bin/quat/dual), and Vanquish Horizon (1500 bar, binary only). For the entire product portfolio, the injection volume is now extended to up to 1000 µL with larger sample loops of 250 µL or 1000 µL. Vanquish Flex and Horizon are biocompatible.

Thermo Scientific Multi-Attribute Method (MAM) Solution:

 Thermo Scientific MAM 2.0 is a single-vendor, end-to-end solution with a fully connected, compliance-ready ecosystem for seamless knowledge sharing on a global scale. This holistic, compliance-ready platform contains tailor-made hardware and software products optimized for development needs and requirements in quality control.

Thermo Scientific Vanquish Method Development Systems: 

Thermo Scientific offers the Vanquish HPLC and UHPLC Systems with Viper Automated Method Scouting Kit, Optional Extension Kit, Chromeleon CDS, and ChromSword, a software package dedicated to the needs of HPLC method development.

Thermo Scientific Application-Specific Vanquish Systems:

 Thermo Fisher Scientific offers Transcend LX and TLX Systems, dual LC or LC–MS, tandem LC or LC–MS, inverse gradient, method development, method transfer, online SPE, and several 2D-LC application systems.

Waters introduced the Acquity Premier and the Arc Premier Systems with MaxPeak High Performance Surfaces Technology. MaxPeak Premier Systems reduce nonspecific absorption of metal‑sensitive analytes such as organic acids, phosphopeptides, antibiotics, organophosphates, phospholipids, glycans, and oligonucleotides. The Acquity Premier System is designed for those who need the ultimate in sensitivity, reproducibility, and speed, and provides the best sensitivity and peak shape for analytical separations. The Arc Premier System is designed for those who need to confidently produce accurate, reliable, and reproducible data. It provides robust results from the first injection reliably and quickly.

Waters BioAccord System with Acquity Premier:

This instalment reviews new HPLC and MS systems, modules, CDS, and other related software, and summarizes their significant features and user benefits.

April 2022 | LCGC Europe

Supercritical Fluid Chromatography for Chiral Analysis, Part 2: Applications

But Why Doesn’t It Get Better? Kinetic Plots for Liquid Chromatography, Part 3: Pulling It All Together

New GC Products for 2021–2022

New HPLC, MS, and CDS Products Introduced in 2021–2022: A Review

Modern Nontargeted Screening (NTS) Methods for Environmental Analysis