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

Comparison of liquid chromatography and supercritical fluidchromatography coupled to compact single quadrupole massspectrometer for targeted in vitro metabolism assay

D.Spaggiari et. al
Journal of Chromatography A, 1371, 244–256 (2014)

Keywords: MS-supported automated method development, In vitro metabolism, Cocktail approach, UHPLC–MS, UHPSFC–MS, Compact single quadrupole


Supercritical fluidchromatography (SFC) was for the first time applied in the context of an in vitro metabolism study. LC and SFC method development procedures were assisted with single quadrupole detector, optimization was performed by computer simulation using DryLab modeling software. Baseline separation of 16 compounds was achieved in both LC and SFC. LOQs of 2–100 ng/mL and 2–200 ng/mL were achieved in LC–MS and SFC–MS, respectively. The compact single quadrupole was successfully used for in vitro metabolism study.

DryLab® optimised two-dimensional high performance liquid chromatography for differentiation of ephedrine and pseudoephedrine based methamphetamine samples

Luke M. Andrighetto; Paul G. Stevenson; James R. Pearson; Luke C. Henderson; Xavier A. Conlan
Forensic Science International, 244, 302-305 (2014)

Keywords: DryLab, Multidimensional high performance liquid chromatography, Ephedrine, Pseudoephedrine, Methamphetamine


In-silico optimised two-dimensional high performance liquid chromatographic (2D-HPLC) separations of a model methamphetamine seizure sample are described, where an excellentmatch between simulated and real separations was observed. DryLab optimisation reduced 2D-HPLC development time significantly. Targeted separation of model compounds was completed with significantly reduced method development time. This separation was completed in the heart-cutting mode of 2D-HPLC where C18 columns were used in both dimensions taking advantage of the selectivity difference of methanol and acetonitrile as the mobile phases. This method development protocol is most significant when optimising the separation of chemically similar chemical compounds as it eliminates potentially hours of trial and error injections to identify the optimised experimental conditions. After only four screening injections the gradient profile for both 2D-HPLC dimensions could be optimised via simulations, ensuring the baseline resolution of diastereomers (ephedrine and pseudoephedrine) in 9.7 min. Depending on which diastereomer is present the potential synthetic pathway can be categorised.

Robust UHPLC Separation Method Development for Multi-API Product Amlodipine and Bisoprolol: The Impact of Column Selection

Róbert Kormány, Imre Molnár, Jenő Fekete, Davy Guillarme, Szabolcs Fekete
Chromatographia, 77, 17-18, 1119-1127 (2014)

Keywords: UHPLC, Method development, Quality by design (QbD), DryLab, Amlodipine, Bisoprolol


A new and fast ultra-high pressure liquid chromatographic separation of amlodipine and bisoprolol and all their closely related compounds is described for impurity profiling purposes. Computer-assisted method development with DryLab was applied and the impact of several state-of- the-art stationary phase column chemistries (50 × 2.1 mm, sub-2 μm, and core–shell type materials) on the achievable selectivity and resolution was investigated. The work was performed according to QbD-principles using design of experiment with three experimental factors: gradient time (tG), temperature (T), and mobile phase pH. DryLab proves that the separation of all compounds was feasible on numerous column chemistries within <10 min, by proper adjustments of variables. It was also demonstrated that the reliability of predictions was good, as the predicted retention times and resolutions were in good agreement with the experimental ones. The final, optimized method separates 16 peaks related to amlodipine and bisoprolol within 7 min, ensuring baseline separation between all peak-pairs.

Rapid UHPLC Method Development for Omeprazole Analysis in a Quality-by-Design Framework and Transfer to HPLC Using Chromatographic Modeling

Schmidt, Alexander H., Stanic, Mijo
LCGC North America, 32, 2, 126-148 (2014)

Keywords: UHPLC, DryLab, QbD, Design Space, Method Development, Method Modeling, Method Transfer, Omeprazole, Impurities


The aim of this study was to apply quality-by-design principles to build in a more scientific and risk-based multifactorial strategy in the development of an ultrahigh-pressure liquid chromatography (UHPLC) method for omeprazole and its related impurities.

The work presents a quality-by-design–based method development strategy for a method that tests the purity of omeprazole. The scientific and risk-based multifactorial method development strategy uses visual chro- matographic modeling as a fast and easy-to-use development tool. To speed up the method development process, all experiments are performed on a UHPLC system. The final method is successfully transferred to HPLC conditions. Predicted and experimental retention times are verified to confirm accuracy of the model.

UHPLC Method Development and Modelling in the Framework of Quality by Design

I. Molnár, H.-J. Rieger, A. Schmidt, J. Fekete, R. Kormány
The Column, 10, 6, 16-21 (2014)


The goals in ultrahigh-pressure liquid chromatography (UHPLC) method development are to first find the best separation, second find the best column, and third find the most robust method in a multifactorial Design Space. Trial and error methods are not sufficient anymore and solid science based on Quality by Design (QbD) principles is required.

Reliability of simulated robustness testing in fast liquid chromatography, using state-of-the-art column technology, instrumentation and modelling software

Kormány, Róbert; Fekete, Jenő; Guillarme, Davy; Fekete, Szabolcs
Journal of Pharmaceutical and Biomedical Analysis, 89, 67-75 (2014)

Keywords: Robustness, UHPLC, DryLab, Method development, Modeling software, Column interchangeability


The goal of this study was to evaluate the accuracy of simulated robustness testing using commercial mod- elling software (DryLab) and state-of-the-art stationary phases. For this purpose, a mixture of amlodipine and its seven related impurities was analyzed on short narrow bore columns (50 × 2.1 mm, packed with sub-2  m particles) providing short analysis times. The performance of commercial modelling software for robustness testing was systematically compared to experimental measurements and DoE based pre- dictions. We have demonstrated that the reliability of predictions was good, since the predicted retention times and resolutions were in good agreement with the experimental ones at the edges of the design space. In average, the retention time relative errors were <1.0%, while the predicted critical resolution errors were comprised between 6.9 and 17.2%. Because the simulated robustness testing requires signif- icantly less experimental work than the DoE based predictions, we think that robustness could now be investigated in the early stage of method development.

Moreover, the column interchangeability, which is also an important part of robustness testing, was investigated considering five different C8 and C18 columns packed with sub-2  m particles. Again, thanks to modelling software, we proved that the separation was feasible on all columns within the same analysis time (less than 4 min), by proper adjustments of variables.

Reliability of computer-assisted method transfer between several column dimensions packed with 1.3–5 µm core–shell particles and between various instruments

Kormány, Róbert; Fekete, Jenő; Guillarme, Davy; Fekete, Szabolcs
Journal of Pharmaceutical and Biomedical Analysis, 94, 188–195 (2014)

Keywords: Method transfer, Method development, DryLab, Modeling software, Core–shell particles


In this contribution, the possibility to automatically transfer RPLC methods between different column dimensions and instruments was evaluated using commercial modelling software. The method transfer reliability was tested with loratadine and its 7 related pharmacopeial impurities. In this study, state- of-the-art columns packed with superficially porous particles of 5, 2.6, 1.7 and 1.3 µm particles were exclusively employed. A fast baseline separation of loratadine and related impurities (Rs,min = 2.49) was achieved under the best analytical conditions (i.e. column of 50 mm × 2.1 mm, 1.3 µm, 10–90% ACN in 5 min, T = 40 ◦ C, pH = 3, F = 0.5 ml/min). This optimal method was successfully tested on columns packed with other particle sizes, namely 1.7 and 2.6 µm, to reduce pressure drop. The selectivities and retentions remained identical, while the peak widths were logically wider, leading to a reduction of peak capacity from 203 to 181 and 159 on the 1.3, 1.7 and 2.6 µm particles, respectively. On the minimum, the reso- lution was equal to 1.54 on the 50 mm × 2.1 mm, 2.6 µm stationary phase. Next to this, the method was transferred to columns of different lengths, inner diameters and particle sizes (100 mm × 3 mm, 2.6 m or 150 mm × 4.6 mm, 5 µm). These columns were used on other LC instruments possessing larger dwell volumes. The modelling software employed for developing the original method was able to calculate the new gradient conditions to be used. The accuracy of prediction was excellent, as the average retention time errors between predicted and observed chromatograms were −0.11% and 0.45% when transferring the method to 100 mm × 3 mm and 150 mm × 4.6 mm columns, respectively. This work proves the use- fulness and validity of HPLC modelling software for transferring methods between different instruments, column dimensions and/or flow rates. 

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