In the field of the quantitative structure–retention and retention–activity relationships (QRAR and QSRR) is crucial to obtain consistent retention factors ( k). For this purpose, two unbiased approaches to estimate k are used: (i) the IUPAC approach (based on the extra-column time correction) and (ii) the ‘2-references’ approach (based on the k estimation respect to two prefixed reference k values). Three reference chemicals were selected attending to their retention time, chemical stability and non-ionic character. Consistent retention factor values for these references were estimated for C 18 chromatographic columns and Brij35 solutions as mobile phases after statistical analysis. The comparison between the k values estimated for a set of 65 test chemicals using the IUPAC and the ‘2-references’ approach shows that the last one gives consistent long-term values useful for QRAR and QSRR modelling purposes.