So far, more than 230 peer reviewed papers have been published on the application of DryLab – a complete list of which you can find here.

DryLab draws on the philosophy described in the three most famous Solvophobic Theory papers IIIIII of Csaba Horváth, which were developed in the years 1975-1977 at Yale University (see also literature by Dr. Imre Molnár).

Read more about the Fundamentals of DryLab and its History.

Keyword Year

Automated UHPLC separation of 10 pharmaceutical compounds using software-modeling

A.Zöldhegyi, H.-J.Rieger, I.Molnár, L.Fekhretdinova
J Pharm Biomed Anal., 156, 15 July, 379-388 (2018)

Keywords: Automated resolution modeling, In-silico method development, Reduction of human error in (U)HPLC, Data integrity, Time efficiency, DryLab


Human mistakes are still one of the main reasons of underlying regulatory affairs that in a compliance with FDA's Data Integrity and Analytical Quality by Design (AQbD) must be eliminated. To develop smooth, fast and robust methods that are free of human failures, a state-of-the-art automation was presented. For the scope of this study, a commercial software (DryLab) and a model mixture of 10 drugs were subjected to testing. Following AQbD-principles, the best available working point was selected and conformational experimental runs, i.e. the six worst cases of the conducted robustness calculation, were performed. Simulated results were found to be in excellent agreement with the experimental ones, proving the usefulness and effectiveness of an automated, software-assisted analytical method development.

Simultaneous optimization of mobile phase composition and pH using retention modeling and experimental design

Norbert Rácz, Imre Molnár, Arnold Zöldhegyi, Hans-Jürgen Rieger, Róbert Kormány
J Pharm Biomed Anal., 160, 25 October 2018, 336-343 (2018)

Keywords: Early-stage robustness calculation, Mobile phase effects, DryLab, Software-assisted method development, UHPLC, HPLC modeling


Chromatographic methods are progressing continuously. Increasing sample complexity and safety expectations lead to higher regulatory demands, hence challenges in liquid chromatography analysis are rising, even today, when faster and faster chromatographic systems are extensively employed and become widely accessible for successful method development.

The goal of this study was to investigate the impact of mobile phase influences as important factors of selectivity tuning in method development. This would mitigate mobile phase-related robustness issues throughout the method's lifecycle.

To discover and understand these effects, a new module of chromatographic modeling software DryLab (ver. 4.3.4. beta) was introduced and a special experimental design (DoE) was tested, allowing the simultaneous optimization of solvent-dependent parameters, such as gradient time (tG), ternary eluent composition (tC) and pH, requiring 18 input experiments (2 × 3 × 3 = 18).

Additionally, the model creation, using a UPLC system and a narrow bore column (50 × 2.1 mm), the entire experimental work could be finished in 2-3 hours. To demonstrate the applicability of this new design, amlodipine and its related pharmacopoeia impurities (A-H) were subjected to be used in a case study. Predicted vs. Experimental (or Verification) runs showed excellent agreement, average retention time deviations were typically less than 1 s. Modelled robustness testing was also performed, elucidating all important mobile phase and instrument parameters that could influence a method's lifetime performance. Furthermore, as the in silico robustness testing is the least time consuming part of the method development process, it can be used extensively to evaluate robustness even at the very early part in stage 1 of the Method Life Cycle (MLC).

Structure assisted impurity profiling for rapid method development in liquid chromatography

Sebastian Schmidtsdorff, Alexander H. Schmidt, Maria Kristina Parr
J. Chromatogr. A, 1577, 23 November, 38–46 (2018)

Keywords: Distribution coefficient (logD), Method development, Quality-by-design (QbD), High-performance liquid chromatography (HPLC), Chromatographic modeling, Extended knowledge space


The use of trial-and-error principles is a frequently used technique in method development. This may lead to the fact that analytical methods are used routinely without developers and users having gained extensive and well-founded knowledge about the robustness of their analytical methods and the influence of critical key parameters. This very often leads to unnecessary problems for analysts. A simple way in reverse phase chromatography to simulate the effects of pH value changes on the separation and retention of substances is the pH-dependent calculation of the logD value. With this tool, model substances were used to show how the time requirement for method screening can be considerably reduced in silico and, in addition, extended knowledge about the separation mechanics can be generated. Based on this knowledge, a new method for the purity analysis of carbamazepine was developed within a very short period of time, which improves the performance of the official Ph.Eur. monograph by far. Furthermore, the extremely high robustness of the new method was demonstrated. Using the logD based approach, Quality-by-Design is applied in method development and kept pace with the increasing requirements of regulatory authorities in the pharmaceutical industry.

Analysis of recombinant monoclonal antibodies in hydrophilic interaction chromatography: A generic method development approach

Balázs Bobály, Valentina D’Atri, Alain Beck, Davy Guillarme, Szabolcs Fekete
J Pharm Biomed Anal., 145, 25 October, 24-32 (2017)

Keywords: HILIC, Method development, Monoclonal antibody, Recovery, Dry Lab


Hydrophilic interaction liquid chromatography (HILIC) is a well-established technique for the separation and analysis of small polar compounds. A recently introduced widepore stationary phase expanded HILIC applications to larger molecules, such as therapeutic proteins. In this paper, we present some generic HILIC conditions adapted for a wide range of FDA and EMA approved recombinant monoclonal antibody (mAb) species and for an antibody-drug conjugate (ADC). Seven approved mAbs possessing various isoelectric point (pI) and hydrophobicity as well as a cysteine conjugated ADC were used in this study. Samples were digested by IdeS enzyme and digests were further fragmented by chemical reduction. The resulting fragments were separated by HILIC. The main benefit of HILIC was the separation of polar variants (glycovariants) in a reasonable analysis time at the protein level, which is not feasible with other chromatographic modes. Three samples were selected and chromatographic conditions were further optimized to maximize resolution. A commercial software was used to build up retention models. Experimental and predicted chromatograms showed good agreement and the average error of retention time prediction was less than 2%. Recovery of various species and sample stability under the applied conditions were also discussed.

Separation of Atropisomers by Chiral Liquid Chromatography and Thermodynamic Analysis of Separation Mechanism

Ling Zhang, Yue Hu, Elizabeth Galella, Frank P. Tomasella, William P. Fish
J Pharm Anal., In Press, Accepted Manuscript (2017)

Keywords: Atropisomer separation, Chiral HPLC, Thermodynamic parameters, β-cyclodextrin stationary phase, Chiral separation mechanism, DryLab, HPLC Method Modeling


In the pharmaceutical industry, the analysis of atropisomers is of considerable interest from a scientific and regulatory perspective. The compound of interest contains two stereogenic axes due to the hindered rotation around the single bonds connecting the aryl groups, which results in four potential configurational isomers (atropisomers). The separation of the four atropisomers is achieved on a derivatized β-cyclodextrin bonded stationary phase. Further investigation shows that low temperature conditions, including sample preparation (−70 °C), sample storage (−70 °C), and chromatographic separation (6 °C), were critical to preventing interconversion. LC-UV-Laser Polarimetric analysis identified peak 1/2 as a pair of enantiomers and peak 3/4 as another. Thermodynamic analysis of the retention data indicated that the separation of the pairs of enantiomers is primarily enthalpy controlled as indicated by the positive slope of the van’t Huff plot. The difference in absolute Δ (Δ H), ranged from 2.20 kJ/mol to 2.42 kJ/mol.

Computer-Assisted Method Development for Small and Large Molecules

Szabolcs Fekete, Róbert Kormány, and Davy Guillarme
LC GC Special Issues, Volume 30, Issue 6, 14–21 (2017)

Keywords: Retention modeling, monoclonal antibodies, antibody drug conjugates, Method development, DryLab, virtual method transfer


The aim of this article is to illustrate the current status of computer-assisted method development and retention modelling. This study focuses on the successful method development of typical small pharmaceutical compounds (impurity profiling) and large therapeutic proteins. By choosing appropriate initial conditions, the method development can be performed in less than one day. However, for small molecules possessing different physicochemical properties, the conditions can be multifarious, while for biopharmaceuticals (for example, monoclonal antibodies [mAbs], antibody–drug conjugates [ADCs]), a generic method can easily be developed. In addition to retention modelling and optimization, the potential of simulated robustness testing is also demonstrated. Depending on the applied retention model, the impact of any change among six experimental parameters (tG, T, pH, ternary composition, flow rate, and initial- and final mobile phase compositions) on the separation can be assessed using a 26 or 36 type virtual factorial design. No additional experiments are required to perform the robustness evaluation. Finally, virtual method transfer between different chromatographic systems is demonstrated.

Separation of antibody drug conjugate species by RPLC: A generic method development approach

Szabolcs Fekete, Imre Molnár, Davy Guillarme
J Pharm Biomed Anal., 137, 15 April, 60-69 (2017)

Keywords: Retention modeling, Antibody drug conjugate, Brentuximab vedotin, Method development, DryLab, Reversed phase liquid chromatography


This study reports the use of modelling software for the successful method development of IgG1 cysteine conjugated antibody drug conjugate (ADC) in RPLC. The goal of such a method is to be able to calculate the average drug to antibody ratio (DAR) of and ADC product. A generic method development strategy was proposed including the optimization of mobile phase temperature, gradient profile and mobile phase ternary composition. For the first time, a 3D retention modelling was presented for large therapeutic protein. Based on a limited number of preliminary experiments, a fast and efficient separation of the DAR species of a commercial ADC sample, namely brentuximab vedotin, was achieved. The prediction offered by the retention model was found to be highly reliable, with an average error of retention time prediction always lower than 0.5% using a 2D or 3D retention models. For routine purpose, four to six initial experiments were required to build the 2D retention models, while 12 experiments were recommended to create the 3D model. At the end, RPLC can therefore be considered as a good method for estimating the average DAR of an ADC, based on the observed peak area ratios of RPLC chromatogram of the reduced ADC sample.

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