title: Determination of nonsteroidal anti-inflammatory drugs in human tear and plasma samples using ultra-fast liquid chromatography-tandem mass spectrometry.
abstract: OBJECTIVE
  To evaluate a new rapid and sensitive method for analyzing human tears and plasma for nonsteroidal anti-inflammatory drugs (NSAIDs) and investigate the influence of the transfer of NSAIDs in an ocular lesion.
  
  
  METHODS
  In this cross-over study, a single dose of 200 mg of ibuprofen and 60 mg of loxoprofen sodium were orally administered to six healthy Japanese subjects. Collected samples were analyzed by ultra-fast liquid chromatography tandem mass spectrometry (UFLC-MS/MS).
  
  
  RESULTS
  Recoveries of the two drugs spiked in the tears and plasma were 96.0-117.0 % in the tears and 99.0-105.7 % in the plasma. Regression equations for both NSAIDs showed excellent linearity from 0.02-1.0 μg/ml for the tears and 0.1-5.0 μg/ml for the plasma, with the limits of detection at 0.02 μg/ml for tears and 0.1 μg/ml for plasma.
  
  
  CONCLUSIONS
  This new high-throughput NSAID determination method only requires a small tear amount (10 μl) and plasma volume (20 μl) and thus will be useful in clinical and toxicological analyses. Analytical results also showed the presence of ibuprofen and loxoprofen in the actual tears and plasma, which confirms the transition of NSAIDs from the tears to the plasma.
authors.affiliation: Department of Ophthalmology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan. mhiro@med.showa-u.ac.jp.|Department of Pharmacology, Showa University School of Medicine, Tokyo, 142-8555, Japan. mhiro@med.showa-u.ac.jp.
authors.forename: Makiko
authors.initials: M
authors.lastname: Hirosawa
authors.affiliation: Department of Pharmacology, Showa University School of Medicine, Tokyo, 142-8555, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sambe
authors.affiliation: Department of Pharmacology, Showa University School of Medicine, Tokyo, 142-8555, Japan.|Clinial Research Institute of Clinical Pharmacology and Therapeutics, Showa University, Tokyo, 157-8577, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Uchida
authors.affiliation: Department of Legal Medicine, Showa University School of Medicine, Tokyo, 142-8555, Japan.
authors.forename: Xiao-Pen
authors.initials: XP
authors.lastname: Lee
authors.affiliation: Department of Legal Medicine, Showa University School of Medicine, Tokyo, 142-8555, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Sato
authors.affiliation: Clinial Research Institute of Clinical Pharmacology and Therapeutics, Showa University, Tokyo, 157-8577, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kobayashi
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D001774:Blood Chemical Analysis; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010666:Phenylpropionates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry; D013666:Tears / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010666:Phenylpropionates; C040656:loxoprofen; D007052:Ibuprofen
keywords: Human tears and plasma; Nonsteroidal anti-inflammatory drugs (NSAIDs); Tandem mass spectrometry (MS/MS)