Simultaneous determination of phenoxyethanol and its major metabolite, phenoxyacetic acid, in rat biological matrices by LC-MS/MS with polarity switching: Application to ADME studies

This study describes the development of a simple LC-ESI-MS/MS method with polarity switching for the simultaneous analysis of phenoxyethanol (PE) and its major metabolite, phenoxyacetic acid (PAA), in rat plasma, urine, and 7 different tissues. The assay was validated to demonstrate the linearity, precision, accuracy, LLOQ recovery, and stability by using the matrix matched QC samples. The assay achieved the LLOQ of 10 and 20 ng/mL of PE and PAA, respectively, for plasma samples and the LLOQ of 20 and 50 ng/mL of PE and PAA, respectively, for urine and tissue samples. This method was successfully applied to the percutaneous absorption, distribution, metabolism, and excretion studies in rats. The absolute topical bioavailability of PE was 75.4% and 76.0% for emulsion and lotion, respectively. Conversion of PE to PAA was extensive, with the average AUC(PAA)-to-AUC(PE) ratio being 4.4 and 5.3 for emulsion and lotion, respectively. The steady-state tissue-to-plasma PE concentration ratio (K-p) was higher than unity for kidney, spleen, heart, brain, and testis and was lower (<= 0.6) for lung and liver, while the metabolite ratio was higher than unity for kidney, liver, lung, and testis and was lower (<= 0.3) for other tissues. Findings of this study may be useful to evaluate the relationship between exposure and toxic potential of PE in risk assessment. (C) 2015 Elsevier B.V. All rights reserved.