Aminoquinolines (AQ) and substituted aminoquinolines (s-AQ) interact with electrochemically monitored supported dioleoyl phosphatidylcholine (DOPC) monolayers and immobilised artificial membranes (IAM) on HPLC column. The electrochemical sensor records adsorption/partition of the compound on and into the layer as well as specific interactions due to the location of the compound in the layer. HPLC-IAM technology measures the partition coefficient between the solution and phospholipid including partition due to interaction of the positive molecular charge with the phospholipid polar heads. The monolayer interaction results were combined and normalised for the neutral compounds’ lipophilicity as a log biomembrane affinity index (‘log BAI’) to exemplify charge and structural features in the interaction. A ChimeraX molecular modelling procedure was used to aid in the results interpretation. A compound ToxScore value was derived from 5 in vitro assays. The ‘log BAI’ exhibited a linear relationship with the AQ pKa values showing that the interaction was related to the molecular positive charge and to the electron donating properties of the –NH2 group. The correlation outliers showed a tendency/no tendency to H-bonding with the polar groups and a superficial/deeper location respectively in the phospholipid layer. The s-AQ ‘log BAI’ value displayed a power correlation with the compounds’ ToxScore values.