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

In silico robustness testing of a compendial HPLC purity method by using of a multidimensional design space build by chromatography modeling — Case study pramipexole

Alexander H. Schmidt, Mijo Stanic, Imre Molnár
J. Pharm. Biomed. Anal., 91, 97-107 (2014)

Keywords: HPLC method development, Quality by Design, Design Space, Robustness in routine quality control, Pramipexole


Purity testing of the active pharmaceutical ingredient (API) pramipexole is performed using an official (compendial) and harmonized method published in the European Pharmacopeia (E.P.) and United States Pharmacopeia (USP). According to this monograph the successful chromatographic separation of the API from impurities is achieved on a C18 column with gradient elution of an ion pairing buffer of pH 3.0 (mobile phase A) and acetonitrile (mobile phase B).

Although not recommended in general, compendial methods are often adapted for purity testing of generic formulations. In this paper a novel approach to evaluate method robustness of an adapted method – prior of full method validation – is described. Based on Quality-by-Design (QbD) principles, a small num- ber of experiments are performed, which after entering them into a chromatography modeling software allow to visualize a multidimensional “Design Space”, a region, in which changes in method parameters will not significantly affect the results as defined in the ICH guideline Q8(R2) leading to a more flexible method handling in routine analysis.

For two different recommended C18 columns a multidimensional Design Space (Method Operating Design Region, MODR) was constructed to study the robustness of the adapted method with a newly developed Robustness Module. In a full factorial design the following six parameters were varied at three levels (low, nominal, high): gradient time, temperature, pH of the aqueous eluent (A), flow rate, start- and end concentration of the organic mobile phase component (eluent B). The resulting 36 = 729 experiments were performed in silico from the previously constructed models for Design Space in less than 1 min and showed that the required resolution of 2.0 could not be reached in all experiments for the two columns which were recommended by the E.P. (failure rate 25% and 16%, respectively). However, by adjusting the gradient time, we were able to fulfill the requirements with a failure rate of zero.

For the aqueous eluent a separate “Eluent Design Space” study was performed, which allows the con- struction of ionic strength vs. ion pairing concentration models to identify the optimum combination of the concentrations for the buffer and the ion-pairing reagent.

Analysis of Sulfonamide Residues in Real Honey Samples using Liquid Chromatography with Fluorescence and Tandem Mass Spectrometry Detection

A. Tölgyesi et. al
J. Liq. Chrom. Rel. Technol., 36, 8, 1105-1125 (2013), DOI: 10.1080/10826076.2012.685911

Keywords: DryLab software, high performance liquid chromatography, food science, honey, kinetex XB HPLC column, optimization, sulfonamides


This paper presents new reversed phase liquid chro-matographic methods (HPLC-FLD and LC-MS/MS) for the quantification of sulfonamides in spiked and incurred honey samples. The sample preparation was optimized using Oasis HLB (hydrophilic–lipophilic balance) solid-phase extraction (SPE) cartridge. Elution of sulfonamides was carried out under acidic, neutral, and basic conditions using methanol. The sample clean-up was also tested using Strata-XL cartridges. The HPLC-FLD separation was performed using a Varian C18 column and a ternary (methanol-acetonitrile-phosphate buffer, pH 5) mobile phase resulting good selectivity for the determination. The robustness of the ternary gradient method was evaluated by computer simulation with DryLab4. LC-MS/MS separation was carried out on a Kinetex XB core-shell type HPLC column that enabled a low limit of detection (0.01–0.5 µg/kg) and faster separation (6 min). The developed methods were validated in accordance with the European Union Commission Decision 2002/657/EC and were applied successfully for more than four hundred honey samples under a national monitoring program.

Application of Quality by Design Principles to a Pharmaceutical Sample Using UHPLC Method Development With Modeling Technologies

Róbert Kormány, Hans-Jürgen Rieger, Imre Molnár
LCGC, 31, 20-27 (2013)


A new type of method development that uses modeling by DryLab4 to find the "best" separation for high performance liquid chromatography (HPLC) was investigated. Principles of Quality by Design (QbD) were followed when planning the investigation. A simple Design of Experiments (DoE) with only three measured factors — gradient time, pH, and temperature — was used with different columns. The basic experiments were saved in an electronic file with the peak tracking results. After calculating a Design Space, the best prediction was compared with a confirmation run. The process delivered precise results and the method was able be transferred to a routine quality control (QC) laboratory.

Optimizing Selectivity During Reversed-Phase HPLC Method Development: Prioritizing Experimental Conditions

L.R. Snyder, J.W. Dolan
 J. Chromatography , 1302, 45–54 (2013)


Several different conditions can be varied to improve selectivity for reversed-phase chromatography (RPC). A reexamination of literature data suggests that changes in selectivity due to a change of column or mobile phase pH are largely replicated by changes in temperature or mobile phase composition (concentrations of acetonitrile and/or methanol). This suggests a reconsideration of the role of mobile phase pH and the column during method development.

Exploring better column selectivity choices in ultra-high performance liquid chromatography using Quality by Design principles

Róbert Kormány, Imre Molnár, Hans-Jürgen Rieger
Journal of Pharmaceutical and Biomedical Analysis, 80, 79-88 (2013)

Keywords: Amlodipine, DoE, DryLab, QbD, UHPLC-column comparison


An older method for amlodipine was reworked with the goal to reduce the analysis time of 60min below 6min. To select the best column for short and robust analysis, 9 different UHPLC column chemistries were investigated using 3-dimensional resolution spaces based on 12 experiments using DryLab4 modelling software. The main variables used were gradient time (tG), temperature (T) and the pH of eluent A. The best critical resolution was calculated and located in a 3-dimensional space in an automated fashion and the corresponding best experiments were carried out. The work (9×12=108 runs) for DryLab4 modeling was finished with an UHPLC instrument in less than 24h. The comparison between predictions and real experiments showed an excellent correlation with differences typically less than 0.04min (<3s) in average, although the set points were located at quite different conditions on gradient times, pH's and temperatures for the individual columns. With the support of DryLab4 all columns could perform the required baseline separation at their individual best working points with satisfactory results.

Determination of alcohols in essential oils by liquid chromatography with ultraviolet detection after chromogenic derivatization

J. Ródenas-Montano, E.J. Carrasco-Correa, M. Beneito-Cambra, G. Ramis-Ramos, J.M. Herrero-Martínez
 J. Chromatography, 1296, 157-163 (2013)

Keywords: Essential oils, Alcohols, Chromogenic derivatization, DryLab, HPLC-UV


An HPLC-UV method to determine compounds having a hydroxyl functional group in plant essential oils is developed. Separation conditions were optimized using the DryLab® method development software, a large sensitivity enhancement was obtained.

Determination of the design space of the HPLC analysis of water-soluble vitamins

H.A. Wagdy, R.S. Hanafi, R.M. El-Nashar, R.M., H.Y. Aboul-Enein
J. Sep. Science, 36, 11, 1703-1710 (2013)

In this work, DryLab is used to accurately determine the design space for critical resolution in the analysis of water-soluble vitamins by HPLC. The multifactorial optimization of three measured parameters (gradient time, temperature, ternary eluent composition (B1/B2)) and seven calculated ones (flow rate, column length, column internal diameter, dwell volume, extracolumn volume, %B [start], and %B [end]) are illustrated. DryLab is used to examine multifactorial effects of these 3+7 parameters on critical resolution and selectivity. Multidimensional robust regions of high critical Rs were defined and graphically verified. The optimum method was selected based on the best resolution separation in the shortest run time. Predicted retention times of all peaks were found to be in excellent match with the virtual ones.

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