title: Determination of 3-methoxysalicylamine levels in mouse plasma and tissue by liquid chromatography-tandem mass spectrometry: application to in vivo pharmacokinetics studies.
abstract: We report the development of a sensitive liquid chromatography-tandem mass spectrometric assay to quantitate 3-methoxysalicylamine (3-MoSA) in biological samples. Derivatization with 1,1'-thiocarbonyldiimidazole followed by C(18) reverse-phase chromatography allowed the detection of both analyte and internal standard (hexylsalicylamine) using electrospray ionization and selected reaction monitoring (SRM) in positive ion mode. We monitored the transitions from m/z 196.7 to 65.1 and from m/z 250.1 to 77.1 for 3-MoSA and HxSA, respectively. The method is validated with respect to linearity (r(2)=0.995), precision (<17% RSD), recovery (100% for 3-MoSA and HxSA), and stability (77% after storage up to 7 month at -80°C). The LOD and LOQ were 16.12 and 48.87 μg/l, respectively and the LLOQ of 1 pg/ml. In addition, we used this assay to analyze the pharmacokinetics of 3-MoSA in mouse plasma and tissues following both intraperitoneal and oral administration, providing new information regarding the distribution of this compound in vivo.
authors.affiliation: Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-6602, USA.
authors.forename: Irene
authors.initials: I
authors.lastname: Zagol-Ikapitte
authors.forename: Venkataraman
authors.initials: V
authors.lastname: Amarnath
authors.forename: Satyawan
authors.initials: S
authors.lastname: Jadhav
authors.forename: John A
authors.initials: JA
authors.lastname: Oates
authors.forename: Olivier
authors.initials: O
authors.lastname: Boutaud
mesh_terms: D000284:Administration, Oral; D000636:Aminosalicylic Acids / Q000008:administration & dosage / Q000032:analysis* / Q000097:blood* / Q000493:pharmacokinetics; D000818:Animals; D001596:Benzylamines / Q000008:administration & dosage / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D007274:Injections, Intraperitoneal; D016014:Linear Models; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution
chemical_list: C560587:3-methoxysalicylamine; D000636:Aminosalicylic Acids; D001596:Benzylamines