Liquid Chromatographic Measurement of Solute Solvent/Solvent Partition Coefficients: Application to Solute/Container Interactions

Abstract

Octanol—water partition coefficients (Po-w) for model compounds used to study solute—polymer interactions are determined by reversed-phase high-performance liquid chromatography (HPLC). Marker compounds of known Po-w are separated using a C8 stationary phase and mobile phases containing varying amounts of methanol, and the capacity factor vs. that methanol content data is used to obtain a capacity factor at 100% water content (log kw). Regression of log kw vs. log Po-w for the markers produces a relationship with an excellent linear correlation (r2 = 0.994). The same procedure is used to obtain log kw (and thus log Po-w) for the polymer—solute interaction model compounds. Hexane-water partition coefficients (Ph-w) for the model compounds are determined by the shake flask method. Polymer—solute interaction constants (Eb) are determined for the interaction between the model solutes and a diethylhexyl phthalate (DEHP) plasticized polyvinyl chloride (PVC) polymer used as a parenteral product container. An interaction model was generated relating the interaction constant to the linear combination of Po-w and Ph-w. For the polymer studied the model takes the form: log Eb = 0.34 log Po-w + 0.29 log Ph-w - 2.39 (r2 = 0.934). The model is used to predict the fractional binding of several common drugs by the container material. The predicted behavior compares favorably with binding data reported in the literature.