title: Simultaneous determination of flurbiprofen and its hydroxy metabolite in human plasma by liquid chromatography-tandem mass spectrometry for clinical application.
abstract: Flurbiprofen (FLB) is one of the phenylalkanoic acid derivatives of non-steroidal anti-inflammatory drugs used for the management of pain and inflammation in patients with arthritis. We developed and validated a rapid and sensitive high-performance liquid chromatography analytical method utilizing tandem mass spectrometry (HPLC-MS/MS) for the simultaneous determination of FLB and its major metabolite, 4'-hydroxyflurbiprofen (4'-OH-FLB), in human plasma. Probenecid was used as an internal standard (IS). After liquid-liquid extraction with methyl t-butyl ether, chromatographic separation of the two analytes was achieved using a reversed-phase Luna C18 column (2.0mm×50mm, 5μm particles) with a mobile phase of 10mM ammonium formate buffer (pH 3.5)-methanol (15:85, v/v) and quantified by MS/MS detection in ESI negative ion mode. The flow rate of the mobile phase was 250μl/min and the retention times of FLB, 4'-OH-FLB, and IS were 1.1, 0.8, and 0.9min, respectively. The calibration curves were linear over a range of 0.01-10μg/ml for FLB and 0.01-1μg/ml for 4'-OH-FLB. The lower limit of quantifications using 100μl of human plasma was 0.01μg/ml for both analytes. The mean accuracy and precision for intra- and inter-run validation of FLB and 4'-OH-FLB were all within acceptable limits. The present HPLC-MS/MS method showed improved sensitivity for quantification of the FLB and its major metabolite in human plasma compared with previously described analytical methods. The validated method was successfully applied to a pharmacokinetic study in humans.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Hye-In
authors.initials: HI
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Goyang 410-820, Republic of Korea.
authors.forename: Chang-Ik
authors.initials: CI
authors.lastname: Choi
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Ji-Yeong
authors.initials: JY
authors.lastname: Byeon
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Se-Hyung
authors.initials: SH
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea; College of Pharmacy, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Yun-Jeong
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Choon-Gon
authors.initials: CG
authors.lastname: Jang
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address: sylee@skku.ac.kr.
authors.forename: Seok-Yong
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001168:Arthritis / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005480:Flurbiprofen / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D011786:Quality Control; D015203:Reproducibility of Results; D056910:Republic of Korea; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C065522:4'-hydroxyflurbiprofen; D005480:Flurbiprofen
keywords: 4′-Hydroxyflurbiprofen; Flurbiprofen; HPLC–MS/MS; Human plasma; Pharmacokinetics