In reversed phase liquid chromatography (RP-LC), the validity of a multiparametric (MP) non-linear least-squares regression iterative method has been evaluated for 14 different aqueous mobile phases modified with one, two or three organic solvents [acetonitrile (ACN), methanol (MeOH), or tetrahydrofuran (THF)] for calculating the retention time of unretained compound t M and the regression parameter (slope b), based on the use of alkan-2-ones and alkyl aryl ketones homologous series. The determination of t M and b has been studied for eight binary (ACN-H 2 O or MeOH-H 2 O), 3 ternary (ACNMeOH-H 2 O) and 3 quaternary (ACN-MeOH-THF-H 2 O) mobile phase systems on an Omnispher C 18 column. The multiparametric calculated t M and b values were compared with those obtained by Guardino's, and Grobler's methods. The MP retention indices (RI) of ten monosubstituted benzenes with different functionality (hydroxyl, carbonyl, nitro, etc.) based on the alkan-2-ones retention index standards have been determined and compared for the different mobile phase compositions studied. The influence of organic modifier type, the nature of mobile phase system and water content on the variation of retention parameter studied in this work were discussed.Keywords Reversed phase-liquid chromatography Á Binary, ternary and quaternary eluent systems Á Multiparametric least-squares adjustment Á Retention time of unretained compound and Retention indices Á Homologous series and monosubstituted benzenes