title: LC-APCI-MS/MS Quantification and Topical Bioavailability of Chloroacetamide in Rats.
abstract: Chloroacetamide (CAA) is a preservative used in various cosmetic, personal care and household products. Due to the hazard potential for allergic reaction and reproductive toxicity, CAA is being considered a high priority for screening assessment and toxicological re-evaluation. This study describes the development of a highly specific and sensitive atmospheric pressure chemical ionization tandem mass spectrometry method for the determination of CAA in rat plasma and its application to a topical bioavailability study. Chromatographic separations were achieved on a C8 column using a highly aqueous mobile phase with a binary gradient elution. The assay was linear in the concentration range of 5-2,500 ng/mL (r ≥ 0.995) using a small sample volume (100 µL). Applicability of the assay was demonstrated in a bioavailability study in rats after i.v. injection (0.5 or 2 mg/kg) and topical application (7.02 mg/kg). Average elimination half-life and clearance ranged from 26.6 to 30.5 min and 53.9 to 57.3 mL/min/kg, respectively. Upon topical application, CAA was slowly but steadily absorbed for a prolonged time period (12 h). The topical bioavailability was 53.5 and 48.3% for emulsion and lotion, respectively. The developed assay may be useful to examine the relationship between exposure and toxic potential of CAA in risk assessment.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeonggi-do 440-746, Korea.
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeonggi-do 440-746, Korea.
authors.forename: Su Hyun
authors.initials: SH
authors.lastname: Seok
authors.affiliation: College of Pharmacy, Dankook University, Cheonan-si, Chungnam 330-714, Korea.
authors.forename: Kyu-Bong
authors.initials: KB
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Gyeongsan-si, Gyeongbuk 712-702, Korea.
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
authors.affiliation: Cosmetics Research Team, Ministry of Food and Drug Safety, Osong-eup, Cheongwon-gun, Chungbuk 363-700, Korea.
authors.forename: Jeong Pyo
authors.initials: JP
authors.lastname: Lee
authors.affiliation: Cosmetics Research Team, Ministry of Food and Drug Safety, Osong-eup, Cheongwon-gun, Chungbuk 363-700, Korea.
authors.forename: Yong-Kyu
authors.initials: YK
authors.lastname: Choi
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeonggi-do 440-746, Korea.
authors.forename: Min Gi
authors.initials: MG
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeonggi-do 440-746, Korea.
authors.forename: Min Kyu
authors.initials: MK
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeonggi-do 440-746, Korea.
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeonggi-do 440-746, Korea sdyoo@skku.ac.kr.
authors.forename: Sun Dong
authors.initials: SD
authors.lastname: Yoo
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000287:Administration, Topical; D000818:Animals; D001682:Biological Availability; D002853:Chromatography, Liquid / Q000379:methods*; D005079:Excipients / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D006207:Half-Life; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000081:Acetamides; D005079:Excipients; C013874:chloroacetamide