title: Pharmacokinetics of diphenylboroxazolidones of L-α-amino acids with activity on the CNS: quantification in rat DBS by UPLC-MS/MS.
abstract: BACKGROUND
  A growing number of boron-containing compounds exhibit many important biological activities; of particular interest are the α-amino acid borinic derivatives with activity in the CNS. A validated, sensitive and specific UPLC-MS/MS technique for quantification of the diphenylboroxazolidones of glycine (DBPX-gly), L-aspartate (DPBX-L-asp) and L-glutamate (DPBX-L-glu) in dried blood spots (DBSs) is presented.
  
  
  RESULTS
  The most intense signal corresponds to compounds with (11)B. The extraction procedure was liquid elution of 3.2-mm punched DBSs with acetonitrile:aqueous formic acid 0.1% (80:20 v/v). Assays proved to be linear, falling accurately and precisely within the range of 0.3-50 µg/ml for DPBX-L-asp and DPBX-L-glu and 0.1-5 µg/ml for DBPX-gly. Chromatograms exhibit clean 2.0-min running time peaks and S/N ratios for the LLOQ were approximately 15:1. The technique was used to evaluate the pharmacokinetics of the molecules and to correlate these with timecourse toxic effects.
  
  
  CONCLUSIONS
  DBSs represent an advantage for the collection of small volumes of samples, and also in terms of processing and storage. UPLC-MS/MS allow us not only to identify the isotopic pattern of boron in DBPX, but also to quantify them with accuracy and specificity. Pharmacokinetics of these molecules exhibit a high apparent volume of distribution; it suggests a preference of DPBX-amino acids for fatty tissues such as the CNS.
authors.affiliation: Department of Physiology, Escuela Nacional de Ciencias Biológicas (ENCB), Instituto Politécnico Nacional (IPN), Mexico City, Mexico.
authors.forename: Alberto García
authors.initials: AG
authors.lastname: González
authors.forename: Leticia Contreras
authors.initials: LC
authors.lastname: Zavala
authors.forename: Alionka P Angeles
authors.initials: AP
authors.lastname: Moreno
authors.forename: Eduardo Ramírez
authors.initials: ER
authors.lastname: San Juan
authors.forename: José G Trujillo
authors.initials: JG
authors.lastname: Ferrara
authors.forename: Liliana Rivera
authors.initials: LR
authors.lastname: Espinosa
authors.forename: Gabriel
authors.initials: G
authors.lastname: Marcelín Jiménez
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D001800:Blood Specimen Collection / Q000379:methods*; D001896:Boron Compounds / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008297:Male; D023303:Oxazolidinones / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000596:Amino Acids; D001896:Boron Compounds; D023303:Oxazolidinones; C060387:boroxazolidone