title: Sensitive liquid chromatography-tandem mass spectrometry method for the simultaneous determination of benzyl butyl phthalate and its metabolites, monobenzyl phthalate and monobutyl phthalate, in rat plasma, urine, and various tissues collected from a toxicokinetic study.
abstract: This study describes the development of a sensitive liquid chromatography-electrospray-tandem mass spectrometry method for the simultaneous determination of benzyl butyl phthalate (BBP) and its major metabolites, monobenzyl phthalate (MBzP) and monobutyl phthalate (MBuP), in rat plasma, urine, and 10 different tissues. The method was validated with regard to the specificity, linearity, precision, accuracy, lower limit of quantification (LLOQ), recovery, and stability by using the matrix-matched quality control samples. The assay achieved LLOQ of 1 ng/ml of BBP for plasma and urine, 4 ng/g for kidney and liver, 10 ng/g for fat, and 20 ng/g for all other tissues. For MBzP and MBuP, the assay achieved LLOQ of 5 ng/ml for plasma and urine, 10 ng/g for fat, and 20 ng/g for all other tissues. The disposition of BBP was characterized by a large volume of distribution (71.1-82.9 l/kg) and a high clearance (838.7-871.0 ml/min/kg). It was extensively metabolized to MBzP and MBuP, with their levels consistently exceeding the BBP levels. The distribution of BBP, MBzP, and MBuP to tissues of kidney, liver, stomach, small intestine, large intestine, spleen, brain, testis, thyroid, and fat was determined under steady-state conditions. For BBP, the steady-state tissue-to-plasma partition coefficient (K p) was the highest for fat (25.0) followed by small intestine (2.6), thyroid (2.0), and stomach (1.1). In contrast, for MBzP and MBuP, it was the highest for kidney (2.0 and 4.3, respectively) and liver (4.3 and 2.1, respectively) but was less than unity for all other tissues. The developed assay method and findings of this study may be useful to evaluate the exposure and toxic potential of BBP and its metabolites in risk assessment.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do, 440-746, South 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, South Korea.
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Gyeongsan, Gyeongbuk, 712-702, South Korea.
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
authors.affiliation: College of Pharmacy, Chonnam National University, Buk-Gu, Gwangju, 500-757, South Korea.
authors.forename: Yong-Bok
authors.initials: YB
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do, 440-746, South 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, South Korea.
authors.forename: Hyeon Gwan
authors.initials: HG
authors.lastname: Choi
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do, 440-746, South Korea.
authors.forename: Youngsung
authors.initials: Y
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do, 440-746, South Korea. sdyoo@skku.ac.kr.
authors.forename: Sun Dong
authors.initials: SD
authors.lastname: Yoo
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D057230:Limit of Detection; D008297:Male; D010795:Phthalic Acids / Q000097:blood / Q000378:metabolism* / Q000633:toxicity / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution; D066007:Toxicokinetics
chemical_list: D010795:Phthalic Acids; C027561:butylbenzyl phthalate; C028577:monobutyl phthalate
keywords: Benzyl butyl phthalate; Liquid chromatography-tandem mass spectrometry; Monobenzyl phthalate; Monobutyl phthalate; Pharmacokinetics; Tissue distribution