Solving Advanced Task-Specific Problems in Measurement Sciences with Generative AI.

The Generative Pre-Trained Transformer known as ChatGPT-4 has undergone extensive pretraining on a diverse data set, enabling it to generate coherent and contextually relevant text based on the input it receives. This capability allows it to perform tasks from answering questions and has attracted significant interest in material sciences, synthetic chemistry, and drug discovery. In this work, we posed four advanced task-specific problems to ChatGPT, which were recently published in leading journals for topics in analytical chemistry, spectroscopy, bioimage super-resolution, and electrochemistry. ChatGPT-4 successfully implemented the four ideas after assigning the "persona" to the AI and posing targeted questions. We show two cases where "unguided" ChatGPT could complete the assignments with minimal human direction. The construction of a microwave spectrum from a free induction curve and super-resolution of bioimages was accomplished using this approach. Two other specific tasks, correcting a complex baseline with morphological operations of set theory and estimating the diffusion current, required additional input, e.g., equations and specific directions from the user. In each case, the MATLAB code was eventually generated by ChatGPT-4 even when the original authors did not provide any code themselves. We show that a validation test must be implemented to detect and correct mistakes made by ChatGPT-4, followed by feedback correction. These approaches will pave the way for open and transparent science and eliminate the black boxes in measurement science when it comes to advanced data processing.

Automated Regularized Deconvolution for Eliminating Extra-Column Effects in Fast High-Efficiency Separations.

With the introduction of ultrahigh efficiency columns and fast separations, the need to eliminate peak deformation contributed by the instrument must be effectively solved. Herein, we develop a robust framework to automate deconvolution and minimize its artifacts, such as negative dips, wild noise oscillations, and ringing, by combining regularized deconvolution and Perona-Malik (PM) anisotropic diffusion methods. A asymmetric generalized normal (AGN) function is proposed to model the instrumental response for the first time. With no-column data at various flow rates, the interior point optimization algorithm extracts the parameters describing instrumental distortion. The column-only chromatogram was reconstructed using the Tikhonov regularization technique with minimal instrumental distortion. For illustration, four different chromatography systems are used in fast chiral and achiral separations with 2.1 and 4.6 mm i.d. columns. Ordinary HPLC data can approach highly optimized UHPLC data. Similarly, in fast HPLC-circular dichroism (CD) detection, 8000 plates were gained for a fast chiral separation. Moment analysis of deconvolved peaks confirms correction of the center of mass, variance, skew, and kurtosis. This approach can be easily integrated and used with virtually any separation and detection system to provide enhanced analytical data.

Symmetrization of Peaks in Chiral Chromatography with an Area-Invariant Resolution Enhancement Method.

A majority of enantiomeric separations show some degree of peak asymmetry, which is detrimental to quantitative and semiquantitative chiral analysis. This paper presents a simple and rapid peak symmetrization algorithm for the correction or reduction of peak tailing or fronting in exponentially modified Gaussians. Raw chromatographic data can be symmetrized by adding a correct fraction of the first derivative to the chromatogram. The area remains invariant since the area under the first derivative is zero for a pure Gaussian and numerically close to zero for asymmetric peaks. A method of easily extracting the distortion parameter is provided, as well as insight into how pre-smoothing the data with the "perfect smoother" algorithm can suppress high frequencies effectively. The central difference method is also used to compute the first derivative, reducing root-mean-square noise by up to 28% compared to the standard forward difference method. A survey of 40 chiral separations is presented, demonstrating the range of asymmetry observed in chiral separations. Examples of symmetrization of the peaks from enantiomers in comparable and disproportionate concentrations are also provided. Artifacts of deconvolution are discussed, along with methods to mitigate such artifacts.

Direct Construction of Peaks from Free Induction Decay Curves for Gas Chromatography-Molecular Rotational Resonance Spectroscopy without Fourier Transforms.

The concept of coupling gas chromatography with molecular rotational resonance spectroscopy (GC-MRR) was introduced in 2020, combining the separation capabilities of GC with the unparalleled specificity of MRR. In this study, we address the challenge of the high data throughput of MRR spectrometers, as GC-MRR spectrometers can generate thousands to millions of data points per second. In the previous GC-MRR studies, a free induction decay (FID) measurement was Fourier transformed to generate each point on the chromatogram. Such extensive calculations limit the performance, sensitivity, and speed of GC-MRR. A direct approach is proposed here to extract peak intensity from FID using the Gram-Schmidt vector orthogonalization method. First, analyte-free FIDs are used to construct a basis set representing the instrument's background noise, and then the remaining FIDs are orthogonalized to this fixed basis set. Each FID yields a single intensity value after Gram-Schmidt orthogonalization. The magnitude of the orthogonalized analyte FID is the signal intensity plotted in the chromatogram. This approach is computationally much faster (up to 10 times) than the conventional Fourier transform algorithm, is at least as sensitive as the FT algorithm, and maintains or improves the chromatographic peak shape. We compare the sensitivity, linearity, and chromatographic peak shapes for the Fourier transform and Gram-Schmidt approaches using both synthetically generated FIDs and instrumental data. This approach would allow the summed peak intensity to be displayed essentially in real-time, following which identified peaks can be further investigated to identify and quantify the species associated with each.

Enhancing Sensitivity for High-Selectivity Gas Chromatography-Molecular Rotational Resonance Spectroscopy.

A next-generation gas chromatograph-molecular rotational resonance (MRR) spectrometer (GC-MRR) with instrumental improvements and higher sensitivity is described. MRR serves as a structural information-rich detector for GC with extremely narrow linewidths and capabilities surpassing 1H nuclear magnetic resonance/Fourier transform infrared spectroscopy/mass spectrometry (MS) while offering unparalleled specificity in regard to a molecule's three-dimensional structure. With a Fabry-Pérot cavity and a supersonic jet incorporated into a GC-MRR, dramatic improvements in sensitivity for molecules up to 244 Da were achieved in the microwave region compared to the only prior work, which demonstrated the GC-MRR idea for the first time with millimeter waves. The supersonic jet cools the analytes to ∼2 K, resulting in a limited number of molecular rotational and vibrational levels and enabling us to obtain stronger GC-MRR signals. This has allowed the limits of detection of the GC-MRR to be comparable to a GC thermal conductivity detector with an optimized choice of gases. The performance of this GC-MRR system is reported for a range of molecules with permanent dipole moments, including alcohols, nitrogen heterocyclics, halogenated compounds, dioxins, and nitro compounds in the molecular mass range of 46-244 Da. The lowest amount of any substance yet detected by MRR in terms of mass is reported in this work. A theoretically unexpected finding is reported for the first time about the effect of the GC carrier gas (He, Ne, and N2) on the sensitivity of the analysis in the presence of the gas driving the supersonic jet (He, Ne, and N2) in the GC-MRR. Finally, the idea of total molecule monitoring in the GC-MRR analogous to selected ion monitoring in GC-MS is illustrated. Structural isomers and isotopologues of bromobutanes and bromonitrobenzenes are used to demonstrate this concept.

Facile Solutions to the Problems Associated with Chemical Information and Mathematical Symbolism While Using Machine Translation Tools.

Advances in computer-aided translation technology have made tremendous progress in accuracy in the past few years. Chemical Abstracts Service of the American Chemical Society summarizes scientific works from more than 50 languages and allows the users to search papers in nine selected languages. Currently, only the abstracts are rendered into English by human experts or by machine translation because full text translation of millions of articles is beyond the human capacity today. An English translation of a research paper, scientific book, or patent is often required for research, data mining, and for historical purposes from various foreign languages. Many fundamental papers in chemistry, quantum chemistry, physics, and mathematics contain a significant number of chemical or mathematical equations. One of the major known problems in machine translation of such symbolically dense texts is incorrect or meaningless output. This article describes how to optimize the existing machine translation tools to read foreign language papers embedded with chemical/mathematical equations. German and French languages have been selected for illustrative purposes for English translation. Direct upload of text with extensive symbolism is possible with certain services, but this also occasionally produces erroneous rendition into English. A facile solution to the associated problems with embedded equations and mathematical formulas is replacing the equations and notations with "dummy" variables. The placeholder or dummy symbols can be removed after translation, and the original equations are substituted again. This approach, which can be automated in future, relies on the idea that chemical formulas and mathematical notations are universal. Following the guidelines in the article, excellent translations can be produced from a text having interspersed equations and chemical symbols.

Improving peak capacities over 100 in less than 60 seconds: operating above normal peak capacity limits with signal processing.

A primary focus in liquid chromatography analysis of complex samples is high peak capacity separations. Using advanced instrumentation and optimal small, high-efficiency columns, complex multicomponent mixtures can now be analyzed in relatively short times. Despite these advances, chromatographic peak overlap is still observed. Recently, attention has shifted from improvements in chromatographic efficiency and selectivity to enhancing data processing after collection. Curve fitting methods can be used to trace underlying peaks, but do not directly enhance chromatographic resolution. Methods based on the properties of derivatives and power transform were recently shown to enhance chromatographic peak resolution while maintaining critical peak information (peak areas and retention times). These protocols have been extensively investigated for their fundamental properties, advantages, and limitations, but they have not been evaluated with complex chromatograms. Herein, we evaluate the use of deconvolution via Fourier transform (FT), even-derivative peak sharpening, and power law with the fast separation (< 60 s) of a 101-component mixture using ultra-high-pressure liquid chromatography. High noise and peak overlap are present in this gradient separation, which is representative of fast chromatography. Chromatographic resolution enhancement is demonstrated and described. Further, accurate quantitation is maintained and shown with representative examples. Enhancements in peak capacity and peak-to-peak resolutions are discussed. Finally, the statistical theory of overlap is used for 101 peaks and predictions are made for the number of singlet, doublet, and multiplets analyte peaks. The effect of increasing peak capacity by FT even derivative sharpening and power laws leads to a decrease in the number of peak overlaps and an increase in total peak number. Graphical abstract.

A Gas Chromatography-Molecular Rotational Resonance Spectroscopy Based System of Singular Specificity.

We designed and demonstrated the unique abilities of the first gas chromatography-molecular rotational resonance spectrometer (GC-MRR). While broadly and routinely applicable, its capabilities can exceed those of high-resolution MS and NMR spectroscopy in terms of selectivity, resolution, and compound identification. A series of 24 isotopologues and isotopomers of five organic compounds are separated, identified, and quantified in a single run. Natural isotopic abundances of mixtures of compounds containing chlorine, bromine, and sulfur heteroatoms are easily determined. MRR detection provides the added high specificity for these selective gas-phase separations. GC-MRR is shown to be ideal for compound-specific isotope analysis (CSIA). Different bacterial cultures and groundwater were shown to have contrasting isotopic selectivities for common organic compounds. The ease of such GC-MRR measurements may initiate a new era in biosynthetic/degradation and geochemical isotopic compound studies.

Ramifications and Insights on the Role of Water in Chiral Sub/Supercritical Fluid Chromatography.

More than 40 cosolvents have been used with carbon dioxide to alter its solvation strength. Among the most interesting systems is the subcritical/supercritical CO2/alkanol eluents. Using small amounts of water in CO2/MeOH is known to be beneficial in chiral subcritical/supercritical chromatography. However, the ramifications of introducing water as a cosolvent component is not entirely understood. In this work, we demonstrate important aspects of the CO2/MeOH/H2O system on nine chiral stationary phases with very different surface chemistries, encompassing derivatized polysaccharides, macrocyclic glycopeptides, iso-butylmercaptoquinine, isopropyl macrocyclic oligosaccharides, and π-electron acceptor/π-electron donor phases. A hydrophilicity scale has been shown to be useful in predicting if a given chiral column chemistry would show a significant enhancement in separation efficiency in the presence of water in the CO2/MeOH system. We demonstrate up to 8-fold enhancements in plate counts of chiral separations with a concomitant decrease in retention times, as predicted by the qualitative test. The same chiral analysis can now be completed in almost a third of the time with the addition of small amounts of water, thereby decreasing organic solvent consumption by a considerable amount. Hydrophobic stationary phases show a minimal increase in efficiency and decrease in analysis times and optimized separations show much larger reduced plate heights, compared to more hydrophilic stationary phases. Furthermore, the presence of water can alter the nature of the adsorption isotherm under nonlinear conditions. Small amounts of water can be used to tune nonlinear tailing peaks into fronting ones, significantly improving preparative enantiomeric separations.

The utility of statistical moments in chromatography using trapezoidal and Simpson's rules of peak integration.

Modern chromatographic data acquisition softwares often behave as black boxes where the researchers have little control over the raw data processing. One of the significant interests of separation scientists is to extract physico-chemical information from chromatographic experiments and peak parameters. In addition, column developers need the total peak shape analysis to characterize the flow profile in chromatographic beds. Statistical moments offer a robust approach for providing detailed information for peaks in terms of area, its center of gravity, variance, resolution, and its skew without assuming any peak model or shape. Despite their utility and theoretical significance, statistical moments are rarely incorporated as they often provide underestimated or overestimated results because of inappropriate choice of the integration method and selection of integration limits. The Gaussian model is universally used in most chromatography softwares to assess efficiency, resolution, and peak position. Herein we present a user-friendly, and accessible approach for calculating the zeroth, first, second, and third moments through more accurate numerical integration techniques (Trapezoidal and Simpson's rule) which provide an accurate estimate of peak parameters as compared to rectangular integration. An Excel template is also provided which can calculate the four moments in three steps with or without baseline correction.

Extending the power transform approach for recovering areas of overlapping peaks.

Power functions, p n ( x ) = [ f ( x ) ] n , are embedded in some modern chromatography detectors and software which not only alter the linear dynamic range of such detectors but also improve the cosmetic aspects of the chromatograms. These aspects include a reduction in baseline noise, improved peak symmetry, and better resolution. However, after raising the electronic output of a detector to a selected power (n > 1), the original peak area information is lost as are very small peaks. Recent advances in the peak processing protocol allow us to recover peak areas from overlapping peak areas, even in noisy environments using power functions. One of the primary protocol requirements of this approach was to have resolution factors ≥0.9. An increasing positive bias in the recovered area was observed as the resolution factors decreased below 0.9. In this work, we extend the capabilities of power function to lower resolution values. This bias is addressed by considering the increasing contributions in peak height coming from adjacent peaks. It is shown that the power function can now be used as long as the peak maxima are visible, making R s  = 0.5, the lower treatable resolution factor for two peaks of similar areas.

Geopolymers as a New Class of High pH Stable Supports with Different Chromatographic Selectivity.

Geopolymers belong to an interesting class of X-ray amorphous polycondensed aluminosilicate ceramic solids. The high mechanical strength, chemical stability in basic conditions, and water insolubility make geopolymers a unique solid support in separation science. This work describes a new straightforward synthetic procedure for making spherical porous geopolymer particles with high surface area which are amenable for chromatographic purposes. In-depth physicochemical evaluation of geopolymers is conducted via particle size distribution, porosity measurements, X-ray diffraction, pH titration, and energy-dispersive spectroscopy and compared with silica, titania, and zirconia. Chromatographic selectivity shows that the surface chemistry of geopolymers has strong hydrophilic and electrostatic character, which makes it different from 36 chromatographic columns. Hydrophilic interaction liquid chromatography in columns packed with geopolymer particles shows different selectivity than that in silica columns, with excellent peak shapes. Phosphate or fluoride additives are not required as they are for zirconia or titania phase.

Separations at the Speed of Sensors.

The virtue of chemical sensors is speed and analyte specificity. The response time to generate an analytical signal typically varies from ∼1 to 20 s, and they are generally limited to a single analyte. Chemical sensors are significantly affected by multiple interferents, matrix effects, temperature, and can vary widely in sensitivity depending on the sensor format. Separation-based analyses remove matrix effects and interferents and are compatible with multiple analytes. However, the speed of such analyses has not been commensurate with traditional sensors until now. Beds of very small size with optimal geometry, containing core-shell particles of judicious immobilized selectors, can be used in an ultrahigh-flow regime, thereby providing subsecond separations of up to 10 analytes. Short polyether ether ketone lined stainless steel columns of various geometries were evaluated to determine the optimal bed geometry for subsecond analysis. Coupling these approaches provides subsecond-based detection and quantitation of multiple chiral and achiral species, including nucleotides, plant hormones, acids, amino acid derivatives, and sedatives among a variety of other compounds. The subsecond separations were reproducible with 0.9% RSD on retention times and showed consistent performance with 0.9% RSD on reduced plate height in van Deemter curves. A new powerful signal processing algorithm is proposed that can further enhance separation outputs and optical spectra without altering band areas on more complex separations such as 10 peaks under a second.

Is Machine Translation a Reliable Tool for Reading German Scientific Databases and Research Articles?

A significant number of published databases and research papers exist in foreign languages and remain untranslated to date. Important sources of primary scientific information in German are Beilstein Handbuch der Organischen Chemie, Gmelin Handbuch der Anorganischen Chemie, Landolt-Börnstein Zahlenwerte und Funktionen, Houben-Weyl Methoden der Organischen Chemie, fundamental research papers, and patents. Although Reaxys has acquired Beilstein and Gmelin, many original references are still in German since 1770s, and the information presented in printed and online versions is often not duplicated. To read these resources, either costly professional translation services are needed or a reading knowledge of German has to be acquired. A convenient approach is to utilize machine translation for reading German texts; however, there is a question of translation reliability. In this work, several different platforms that employ neural network for machine translation (NMT) were tested for translation capability of scientific German. From a preliminary survey, Google Translate and DeepL were finalized for further studies (German to English). Excerpts from German documents spanning more than a century have been carefully chosen from standard works. DeepL Translator and Google Translate were found to be reliable for converting German scientific literature into English for a wide variety of technical passages. As a benchmark, human and machine translations are compared for complex sentences from old literature and a recent publication. Care and intuition should be used before relying on machine translation of methods and directions in general. Reagent addition (to or from) may be inverted in some synthetic procedures using machine translations.

Fundamental and Practical Insights on the Packing of Modern High-Efficiency Analytical and Capillary Columns.

New stationary phases are continuously developed for achieving higher efficiencies and unique selectivities. The performance of any new phase can only be assessed when the columns are effectively packed under high pressure to achieve a stable bed. The science of packing columns with stationary phases is one of the most crucial steps to achieve consistent and reproducible high-resolution separations. A poorly packed column can produce non-Gaussian peak shapes and lower detection sensitivities. Given the ever larger number of stationary phases, it is impossible to arrive at a single successful approach. The column packing process can be treated as science whose unified principles remain true regardless of the stationary phase chemistry. Phenomenologically, the column packing process can be considered as a constant pressure or constant flow high-pressure filtration of a suspension inside a column with a frit at the end. This process is dependent on the non-Newtonian suspension rheology of the slurry in which the particles are dispersed. This perspective lays out the basic principles and presents examples for researchers engaged in stationary phase development. This perspective provides an extensive set of slurry solvents, hardware designs, and a flowchart, a logical approach to optimal column packing, thus eliminating the trial and error approach commonly practiced today. In general, nonaggregating but high slurry concentrations of stationary phases tend to produce well packed analytical columns with small particles. Conversely, C18 packed capillary columns are best packed using agglomerating solvents.

Salient Sub-Second Separations.

Sub-second liquid chromatography in very short packed beds is demonstrated as a broad proof of concept for chiral, achiral, and HILIC separations of biologically important molecules. Superficially porous particles (SPP, 2.7 µm) of different surface chemistries, namely, teicoplanin, cyclofructan, silica, and quinine, were packed in 0.5-cm-long columns for separating different classes of compounds. Several issues must be addressed to obtain the maximum performance of 0.5 cm columns with reduced plate heights of 2.6 to 3.0. Modified UHPLC hardware can be used to obtain sub-second separations provided extra-column dispersion is minimized and sufficient data acquisition rates are used. Further, hardware improvements will be needed to take full advantage of faster separations. The utility of power transform, which is already employed in certain chromatography detectors, is shown to be advantageous for sub-second chromatography. This approach could prove to be beneficial in fast screening and two-dimensional liquid chromatography.

Instrumental Idiosyncrasies Affecting the Performance of Ultrafast Chiral and Achiral Sub/Supercritical Fluid Chromatography.

It is widely accepted that column technology is ahead of existing chromatographic instruments. The chromatographic output may not reflect the true picture of the peak profile inside the column. The instrumental optimization parameters become far more important when peaks elute in a few seconds. In this work, the low viscosity advantage of the supercritical/subcritical CO2 is coupled with the high efficiency of narrow particle size distribution silica. Using short efficient columns and high flow rates (up to 19 mL/min), separations on the order of a few seconds are demonstrated. In the domain of ultrafast supercritical fluid chromatography (SFC), unexpected results are seen which are absent in ultrafast liquid chromatography. These effects arise due to the compressible nature of the mobile phase and detector idiosyncrasies to eliminate back-pressure regulator noise. We demonstrate unusual connection tubing effects with 50, 75, 127, 254, and 500 µm tubings and show the complex relation of dead time, retention time, efficiency, and optimum velocity with the tubing diameter (via column outlet pressure). Fourier analysis at different back-pressure regulator (BPR) settings shows that some instruments have very specific noise frequencies originating from the BPR, and those specific frequencies vanish under certain conditions. The performance of embedded digital filters, namely, moving average, numerically simulated low pass RC, and Gaussian kernels, is compared. This work also demonstrates, using a simple derivative test, that some instruments employ interpolation techniques while sampling at "true" low frequencies to avoid picking up high frequency noise. Researchers engaged in ultrafast chromatography need to be aware of the instrumental nuances and optimization procedures for achieving ultrafast chiral or achiral separations in SFC mode.

Gone in seconds: praxis, performance, and peculiarities of ultrafast chiral liquid chromatography with superficially porous particles.

A variety of brush-type chiral stationary phases (CSPs) were developed using superficially porous particles (SPPs). Given their high efficiencies and relatively low back pressures, columns containing these particles were particularly advantageous for ultrafast "chiral" separations in the 4-40 s range. Further, they were used in all mobile phase modes and with high flow rates and pressures to separate over 60 pairs of enantiomers. When operating under these conditions, both instrumentation and column packing must be modified or optimized so as not to limit separation performance and quality. Further, frictional heating results in axial thermal gradients of up to 16 °C and radial temperature gradients up to 8 °C, which can produce interesting secondary effects in enantiomeric separations. It is shown that the kinetic behavior of various CSPs can differ from one another as much as they differ from the well-studied C18 reversed phase media. Three additional interesting aspects of this work are (a) the first kinetic evidence of two different chiral recognition mechanisms, (b) a demonstration of increased efficiencies at higher flow rates for specific separations, and

Peak distortion effects in analytical ion chromatography.

The elution profile of chromatographic peaks provides fundamental understanding of the processes that occur in the mobile phase and the stationary phase. Major advances have been made in the column chemistry and suppressor technology in ion chromatography (IC) to handle a variety of sample matrices and ions. However, if the samples contain high concentrations of matrix ions, the overloaded peak elution profile is distorted. Consequently, the trace peaks shift their positions in the chromatogram in a manner that depends on the peak shape of the overloading analyte. In this work, the peak shapes in IC are examined from a fundamental perspective. Three commercial IC columns AS16, AS18, and AS23 were studied with borate, hydroxide and carbonate as suppressible eluents. Monovalent ions (chloride, bromide, and nitrate) are used as model analytes under analytical (0.1 mM) to overload conditions (10-500 mM). Both peak fronting and tailing are observed. On the basis of competitive Langmuir isotherms, if the eluent anion is more strongly retained than the analyte ion on an ion exchanger, the analyte peak is fronting. If the eluent is more weakly retained on the stationary phase, the analyte peak always tails under overload conditions regardless of the stationary phase capacity. If the charge of the analyte and eluent anions are different (e.g., Br(-) vs CO3(2-)), the analyte peak shapes depend on the eluent concentration in a more complex pattern. It was shown that there are interesting similarities with peak distortions due to strongly retained mobile phase components in other modes of liquid chromatography.

Influence of theoretical and semi-empirical peak models on the efficiency calculation in chiral chromatography.

Height equivalent to theoretical plate (H) equations, such as the van Deemter or Knox-Saleem equations, and other efficiency vs. linear velocity equations (u), provide kinetic insights into chromatographic separations phenomena and column performance. In enantioselective separations, the peak shape of the two enantiomers can differ significantly and are often asymmetric. The peak efficiency calculations heavily impact these efficiency-flow profiles, leading to erroneous estimations of eddy diffusion, longitudinal diffusion, and mass transfer terms. In this work, new asymmetric peak functions are employed for modeling enantiomer peaks based on the Haarhoff-Van der Linde function, its generalized variant (GHVL), once Generalized Asymmetric Gaussian (AGN), and Twice Generalized Gaussian (TGN). The new models (AGN, TGN, and GHVL) incorporate higher statistical moments besides the zeroth, first, and second moments to account for two-sided asymmetry (fronting or tailing). The fit results are compared with the traditional efficiency calculation methods endorsed by official pharmacopeia and numerical estimation of moments from the raw data. Enantiomeric separations of ibuprofen and dl-homophenylalanine were chosen as probe molecules. The results demonstrate that non-linear least squares fitted functions provide better estimations of peak efficiency data even in the presence of high noise. In particular, the generalized models consistently offered the best quality fits for various peak shapes in chiral separations. Conversely, the half-height Gaussian method greatly overpredicted skewed peak efficiencies. This investigation reveals that the commonly held assumptions of peak shape and numerical integration of raw data are highly insufficient for chiral chromatography. The impact of asymmetry on plate height should not be overlooked when accurate data from efficiency-flow rate curves is derived. We advocate for the broader adoption of these new generalized peak (AGN, TGN, GHVL) models because they provide robustness at various SNRs that account for right or left asymmetry while accurately representing peak geometry.