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

• A simulated method transfer was systematically evaluated.
• Predicted retention times were experimentally verified.
• Equivalent separations could be performed on several column dimensions.
• Modelling software could be useful tools in early stage method development.
• Important time and solvent saving can be achieved with the proposed approach.

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 resolution 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 μm 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 usefulness and validity of HPLC modelling software for transferring methods between different instruments, column dimensions and/or flow rates.

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