title: 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.
abstract: 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 AUCPAA-to-AUCPE ratio being 4.4 and 5.3 for emulsion and lotion, respectively. The steady-state tissue-to-plasma PE concentration ratio (Kp) was higher than unity for kidney, spleen, heart, brain, and testis and was lower (≤0.6) for lung and liver, while the metabolite Kp 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.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Min Gi
authors.initials: MG
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Min Gyu
authors.initials: MG
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Gyeongsan, Gyeongbuk, Republic of Korea.
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
authors.affiliation: College of Pharmacy, Dankook University, Cheonan, Chungnam, Republic of Korea.
authors.forename: Kyu-Bong
authors.initials: KB
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Jong Bong
authors.initials: JB
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Soo Heui
authors.initials: SH
authors.lastname: Paik
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea. Electronic address: sdyoo@skku.ac.kr.
authors.forename: Sun Dong
authors.initials: SD
authors.lastname: Yoo
mesh_terms: D065966:Absorption, Physicochemical; D000085:Acetates / Q000008:administration & dosage / Q000032:analysis* / Q000378:metabolism* / Q000493:pharmacokinetics; D053000:Analytic Sample Preparation Methods; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D005026:Ethylene Glycols / Q000008:administration & dosage / Q000032:analysis* / Q000378:metabolism* / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000085:Acetates; D005026:Ethylene Glycols; C005398:phenoxyethanol; C415326:phenoxyacetic acid
keywords: Distribution; Elimination; LC–MS/MS; Percutaneous absorption; Phenoxyacetic acid; Phenoxyethanol