title: Determination of tigecycline in human skin using a novel validated LC-MS/MS method.
abstract: BACKGROUND
  To develop and validate a sensitive and novel bioanalytical method for measuring tigecycline concentrations in human skin using LC-MS/MS.
  
  
  RESULTS
  The method utilizes addition of a stabilizing agent to the human skin or surrogate (human liver or rat skin), homogenization of human skin in a strong acidic-methanol extraction solvent, centrifugation of the skin suspension, filtration of the skin suspension supernatant, separation by LC (Polaris™ C18-A 50 × 2.0 mm), and detection of tigecycline by MS/MS. Linearity was 50-20,000 ng/g, using a sample size of 100 mg. The intra-and inter-day accuracy and precision of the assay met acceptance criteria.
  
  
  CONCLUSIONS
  This method has been successfully applied to 17 incurred human skin samples from volunteers with surgical infections who received intravenous doses of tigecycline (100 mg initial loading dose and 50 mg every 12 h for at least 2 days). Tigecycline concentrations in these samples ranged from 185 to 2853 ng/g.
authors.affiliation: Bioanalytical R&D, Wyeth Research, Pearl River, NY 10965, USA. jia@wyeth.com
authors.forename: Allena
authors.initials: A
authors.lastname: Ji Ji
authors.forename: James Patrick
authors.initials: JP
authors.lastname: Saunders
authors.forename: Peter
authors.initials: P
authors.lastname: Amorusi
authors.forename: Gary
authors.initials: G
authors.lastname: Stein
authors.forename: Nandan Dilip
authors.initials: ND
authors.lastname: Wadgaonkar
authors.forename: Kenneth Patrick
authors.initials: KP
authors.lastname: O'Leary
authors.forename: Mauricio
authors.initials: M
authors.lastname: Leal
authors.forename: Eric Norbert
authors.initials: EN
authors.lastname: Fluhler
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000032:analysis*; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D008099:Liver / Q000737:chemistry; D008911:Minocycline / Q000031:analogs & derivatives* / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000737:chemistry*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D008911:Minocycline