title: DBS-LC-MS/MS assay for caffeine: validation and neonatal application.
abstract: OBJECTIVE
  DBS might be an appropriate microsampling technique for therapeutic drug monitoring of caffeine in infants. Nevertheless, its application presents several issues that still limit its use. This paper describes a validated DBS-LC-MS/MS method for caffeine.
  
  
  RESULTS
  The results of the method validation showed an hematocrit dependence. In the analysis of 96 paired plasma and DBS clinical samples, caffeine levels measured in DBS were statistically significantly lower than in plasma but the observed differences were independent from hematocrit.
  
  
  CONCLUSIONS
  These results clearly showed the need for extensive validation with real-life samples for DBS-based methods. DBS-LC-MS/MS can be considered to be a good alternative to traditional methods for therapeutic drug monitoring or PK studies in preterm infants.
authors.affiliation: Department of Paediatrics, Skane University Hospital, Lund University, Lund, Sweden.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bruschettini
authors.affiliation: Clinical Pathology Laboratory Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Barco
authors.affiliation: Department of Paediatrics, Skane University Hospital, Lund University, Lund, Sweden.
authors.forename: Olga
authors.initials: O
authors.lastname: Romantsik
authors.affiliation: Neonatal Intensive Care Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Risso
authors.affiliation: Clinical Pathology Laboratory Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Iulian
authors.initials: I
authors.lastname: Gennai
authors.affiliation: IBIS Informatica, Milan, Italy.
authors.forename: Benito
authors.initials: B
authors.lastname: Chinea
authors.affiliation: Neonatal Intensive Care Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Luca A
authors.initials: LA
authors.lastname: Ramenghi
authors.affiliation: Clinical Pathology Laboratory Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Gino
authors.initials: G
authors.lastname: Tripodi
authors.affiliation: Clinical Pathology Laboratory Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Cangemi
mesh_terms: D001049:Apnea / Q000188:drug therapy; D002110:Caffeine / Q000097:blood*; D000697:Central Nervous System Stimulants / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods; D059788:Dried Blood Spot Testing / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D006400:Hematocrit; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood*; D057230:Limit of Detection; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000697:Central Nervous System Stimulants; D002110:Caffeine
keywords: DBS; LC–MS/MS; PK; caffeine; newborn; preterm; therapeutic drug monitoring