title: Simultaneous quantification of naproxcinod and its active metabolite naproxen in rat plasma using LC-MS/MS: application to a pharmacokinetic study.
abstract: In this study, a liquid chromatography-tandem mass spectrometry method was developed and validated to simultaneously determine naproxcinod and naproxen concentrations in rat plasma for the first time. Plasma samples were prepared by simple one-step extraction with methanol for protein precipitation using only 50 μL plasma. Separation was performed on a Synergi Fusion-RP C18 column with a run time of 4 min. Naproxcinod, naproxen and internal standard concentrations were detected in the positive ion mode using multiple reaction monitoring (MRM) of the transitions at m/z 348.2→302.2, 231.1→185.1 and 271.2→203.1, respectively. The calibration curves were linear, with all correlation coefficients being ≥0.9952, in the range of 1.00-400 ng/mL for naproxcinod and 20.0-8000 ng/mL for naproxen. Their accuracy was in the range of -8.1% to 8.7%, and the intra- and inter-day variations were ≤4.53%. The mean extraction recovery of all analytes was more than 93.1% efficient. Stability testing showed that naproxcinod and naproxen remained stable during the whole analytical procedure. After validation, the method was successfully applied to a pharmacokinetic study of naproxcinod and naproxen in rats. The AUC0-∞ of naproxen was 74.6 times larger than that of naproxcinod, which indicated that naproxcinod was rapidly metabolized into naproxen in rats.
authors.affiliation: School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Shi
authors.affiliation: School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Weiding
authors.initials: W
authors.lastname: Shang
authors.affiliation: School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Engineering, Hebei Chemical and Pharmaceutical College, Shijiazhuang 050026, China.
authors.forename: Na
authors.initials: N
authors.lastname: Xue
authors.affiliation: Department of Pharmaceutical Engineering, Hebei Chemical and Pharmaceutical College, Shijiazhuang 050026, China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Hao
authors.affiliation: School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Yabo
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Second Hospital, Hebei Medical University, Shijiazhuang 050000, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Sun
authors.affiliation: School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Du
authors.affiliation: School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Deying
authors.initials: D
authors.lastname: Cao
authors.affiliation: School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, China. Electronic address: zhk810728@163.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang 050017, China. Electronic address: shiqingwen@hebmu.edu.cn.
authors.forename: Qingwen
authors.initials: Q
authors.lastname: Shi
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D016014:Linear Models; D008297:Male; D009288:Naproxen / Q000031:analogs & derivatives* / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C111751:naproxen-n-butyl nitrate; D009288:Naproxen
keywords: LC–MS/MS; Naproxcinod; Naproxen; Pharmacokinetic study