Intelligent automation of high-performance liquid chromatography method development by means of a real-time knowledge-based approach

I, Ting-Po; Smith, Randy; Guhan, Sam; Taksen, Ken; Vavra, Mark; Myers, Douglas R.; Hearn, Milton Thomas William

doi:10.1016/s0021-9673(02)01075-0

Cited by 27 publications

(4 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7. As discussed elsewhere (19), automation of the selection of buffer compositions in RP–HPLC, CZE and CEC can be achieved using an approach based on real‐time knowledge‐based artificial intelligence systems, facilitating the optimization of resolution of complex mixtures of synthetic peptides.…”

Section: Influence Of the Acetonitrile Contentmentioning

confidence: 99%

The CEC behaviour of several synthetic peptides related to the activin β_A–β_D subunits

Walhagen¹,

Boysen

Hearn

et al. 2003

The Journal of Peptide Research

View full text Add to dashboard Cite

The resolution of several structurally related synthetic peptides, derived from the loop 3 region of the activin betaA-betaD subunits, has been studied using capillary electrochromatography (CEC) with Hypersil n-octadecylsilica as the sorbent. The results confirm that the CEC migration of these peptides can be varied in a charge-state-specific manner as the properties of the background electrolyte, such as pH, salt concentration and content of organic modifier, or temperature are systematically changed. Acidic peptides followed similar trends in retention behaviour, which was distinctly different to that shown by more basic peptides. The CEC separation of these peptides with the Hypersil n-octadecyl-silica involved distinguishable contributions from both electrophoretic mobility and chromatographic retention. Temperature effects were reflected as variations in both the electro-osmotic flow and the electrophoretic mobility of the peptides. When the separation forces acting on the peptides were synergistic with the electro-osmotic flow, as, for example, with the positively charged peptides at a particular pH and buffer electrolyte composition, their retention coefficient, kappacec, decreased with increasing capillary temperature, whereas when the separation forces worked in opposite directions, as for example with negatively charged peptides, their kappacec values increased slightly with increasing temperature. Moreover, when the content of organic modifier, acetonitrile, was sufficiently high, e.g. > 40% (v/v) and nonpolar interactions with the Hypersil n-octadecyl-silica sorbent were suppressed, mixtures of both the basic and acidic synthetic peptides could be baseline resolved under isocratic conditions by exploiting the mutual processes of electrophoretic mobility and electrostatic interaction. A linear relationship between the ln kappacec values and the volume fractions, psi, of the organic modifier over a limited range of psi-values, was established for the negatively charged peptides under these isocratic conditions. These findings thus provide useful guidelines in a more general context for the resolution and analysis of structurally related synthetic peptides using CEC methods.

show abstract

Section: Influence Of the Acetonitrile Contentmentioning

confidence: 99%

The CEC behaviour of several synthetic peptides related to the activin β_A–β_D subunits

Walhagen¹,

Boysen

Hearn

et al. 2003

The Journal of Peptide Research

View full text Add to dashboard Cite

show abstract

“…Such strategies are not new. Indeed, I and co-workers investigated the use of decision trees for LC optimization for four pharmaceutical compounds . The group of Kell published their robot chromatographer system for gas chromatography (GC)–MS in metabolomics , and later extended it for a one-step optimization for LC–MS .…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, I and co-workers investigated the use of decision trees for LC optimization for four pharmaceutical compounds. 21 The group of Kell published their robot chromatographer system for gas chromatography (GC)–MS in metabolomics 22 , 23 and later extended it for a one-step optimization for LC–MS. 24 Their solution utilized a PESA-II genetic multiobjective optimization algorithm operated using a combination of Microsoft Excel and mouse-click macros.…”

Section: Introductionmentioning

confidence: 99%

Chemometric Strategies for Fully Automated Interpretive Method Development in Liquid Chromatography

et al. 2022

View full text Add to dashboard Cite

The majority of liquid chromatography (LC) methods are still developed in a conventional manner, that is, by analysts who rely on their knowledge and experience to make method development decisions. In this work, a novel, open-source algorithm was developed for automated and interpretive method development of LC(−mass spectrometry) separations (“AutoLC”). A closed-loop workflow was constructed that interacted directly with the LC system and ran unsupervised in an automated fashion. To achieve this, several challenges related to peak tracking, retention modeling, the automated design of candidate gradient profiles, and the simulation of chromatograms were investigated. The algorithm was tested using two newly designed method development strategies. The first utilized retention modeling, whereas the second used a Bayesian-optimization machine learning approach. In both cases, the algorithm could arrive within 4–10 iterations (i.e., sets of method parameters) at an optimum of the objective function, which included resolution and analysis time as measures of performance. Retention modeling was found to be more efficient while depending on peak tracking, whereas Bayesian optimization was more flexible but limited in scalability. We have deliberately designed the algorithm to be modular to facilitate compatibility with previous and future work (e.g., previously published data handling algorithms).

show abstract

“…To speed up this work, fully or semiautomated MD software has been developed over the years. − Roughly spoken, the automated MD strategies described in literature are either search-based (e.g., using the Simplex method) or model-based (e.g., Drylab, Chromsword) . In the present study, the properties of a hybrid method, further referred to as the predictive elution window stretching and shifting method (PEWS 2 ), were investigated.…”

mentioning

confidence: 99%

Predictive Elution Window Stretching and Shifting as a Generic Search Strategy for Automated Method Development for Liquid Chromatography

et al. 2012

View full text Add to dashboard Cite

ABSTRACT:We report on the possibilities of a new method development (MD) algorithm that searches the chromatographic parameter space by systematically shifting and stretching the elution window over different parts of the time-axis. In this way, the search automatically focuses on the most promising areas of the solution space. Since only the retention properties of the first and last eluting compounds of the sample need to be (approximately) known, the algorithm can be directly applied to samples with unknown composition, and the proposed solutions are not sensitive to any modeling errors. The search efficiency of the algorithm has been evaluated on an extensive set of random-generated in silico samples covering a broad range of different retention properties. Compared to a pure grid-based search, the algorithm could reduce the number of missed components by 50% and more. The algorithm has also been applied to solve three different real-world separation problems from the pharmaceutical industry. All problems could be successfully solved in a very short time (order of 12 h of instrument time).O ne of the most time-consuming tasks in analytical liquid chromatography is method development (MD). This is the search for the chromatographic operating conditions (type of organic modifier and stationary phase, temperature, gradient profile, pH, ionic strength, etc.) leading to the complete resolution of the sample in all its individual constituents. 1−9 Because of the high probability for peak overlap 10 and the sensitive dependency of the retention time of the individual analytes on, for example, the employed gradient slope, the MD process still involves a lot of trial and error and can take up to several weeks of work.To speed up this work, fully or semiautomated MD software has been developed over the years. 10−16 Roughly spoken, the automated MD strategies described in literature are either search-based (e.g., using the Simplex method) 17 or modelbased (e.g., Drylab, 18 Chromsword). 19 In the present study, the properties of a hybrid method, further referred to as the predictive elution window stretching and shifting method (PEWS 2 ), were investigated. This method explores the chromatographic parameter space in a pure search-mode but also uses the information on the retention properties of some of the peaks (e.g., the first and the last peak of the chromatogram and/or the first and last peaks of its most problematic zone). This information is used to make a model-based prediction of the gradient slope (expressed here as βt 0 = (ϕ e − ϕ 0 )·t 0 /t G ) and initial gradient composition ϕ 0 values that should be imposed to shift and stretch the elution window of the sample in a controlled manner over different parts of the time-axis. Hence, instead of optimizing the gradient by searching in the (ϕ 0 ,βt 0 )-space, the PEWS 2 -method searches directly in the (k first ,k last )-space. Since the values of k first and k last directly determine how wide the elution window is and whether the components elute early or late, t...

show abstract

Intelligent automation of high-performance liquid chromatography method development by means of a real-time knowledge-based approach

Cited by 27 publications

References 36 publications

The CEC behaviour of several synthetic peptides related to the activin β_A–β_D subunits

The CEC behaviour of several synthetic peptides related to the activin β_A–β_D subunits

Chemometric Strategies for Fully Automated Interpretive Method Development in Liquid Chromatography

Predictive Elution Window Stretching and Shifting as a Generic Search Strategy for Automated Method Development for Liquid Chromatography

Contact Info

Product

Resources

About

Intelligent automation of high-performance liquid chromatography method development by means of a real-time knowledge-based approach

Cited by 27 publications

References 36 publications

The CEC behaviour of several synthetic peptides related to the activin βA–βD subunits

The CEC behaviour of several synthetic peptides related to the activin βA–βD subunits

Chemometric Strategies for Fully Automated Interpretive Method Development in Liquid Chromatography

Predictive Elution Window Stretching and Shifting as a Generic Search Strategy for Automated Method Development for Liquid Chromatography

Contact Info

Product

Resources

About

The CEC behaviour of several synthetic peptides related to the activin β_A–β_D subunits

The CEC behaviour of several synthetic peptides related to the activin β_A–β_D subunits