title: Quantification of piroxicam and 5'-hydroxypiroxicam in human plasma and saliva using liquid chromatography-tandem mass spectrometry following oral administration.
abstract: Saliva sampling used to quantify piroxicam and 5'-hydroxypiroxicam is a noninvasive and painless method when compared to sequential blood sampling. For that, a rapid, selective and sensitive liquid chromatography-tandem mass spectrometric method for simultaneous determination of piroxicam and 5'-hydroxypiroxicam in saliva and human plasma was developed and validated. Piroxicam and its major metabolite were separated using a LiChroCART 125-4 RP Select-B Sorbent C18 column using a mixture of methanol and 2% phosphoric acid (pH 2.7) (70:30, v/v) for the mobile phase with a flow injection of 1mL/min. The run time was 4min. Volunteers had saliva and blood sampled before, 1, 2, 3, 4, 5, 6, 8, 11, 24, 48 and 72h after taking a 20mg oral dose of piroxicam. The pharmacokinetic parameters of piroxicam in plasma samples were as follows: AUC0-72 (64819hng/mL), predicted clearance (0.2L/h), distribution volume (14.8L), elimination half-life (50.7h) and saliva/plasma concentration ratio (0.003). The estimation of all pharmacokinetic parameters for 5'-hydroxypiroxicam would require collections beyond 72h; however, it was possible to quantify the mean maximum concentration (133ng/mL), time to peak concentration (53.6h), mean AUC0-72 (6213hng/mL), predicted clearance (110.3L/h) and saliva/plasma concentration ratio (0.04). The developed methods proved effective and sensitive for determining the lower quantification limit of piroxicam in plasma (6.1ng/mL) and saliva (0.15ng/mL) and of 5'-hydroxypiroxicam in plasma (1.2ng/mL) and saliva (0.15ng/mL).
authors.affiliation: Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Brazil.
authors.forename: Adriana Maria
authors.initials: AM
authors.lastname: Calvo
authors.affiliation: Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Brazil.
authors.forename: Gabriel Mulinari
authors.initials: GM
authors.lastname: Santos
authors.affiliation: Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Brazil.
authors.forename: Thiago José
authors.initials: TJ
authors.lastname: Dionísio
authors.affiliation: Department of Clinical, Toxicologic and Bromatologic Analyses, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil.
authors.forename: Maria Paula
authors.initials: MP
authors.lastname: Marques
authors.affiliation: Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Brazil.
authors.forename: Daniel Thomas
authors.initials: DT
authors.lastname: Brozoski
authors.affiliation: Department of Clinical, Toxicologic and Bromatologic Analyses, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil.
authors.forename: Vera Lúcia
authors.initials: VL
authors.lastname: Lanchote
authors.affiliation: Laboratory for Bone Metabolism and Regeneration, Faculty of Dentistry, University of Porto, Portugal.
authors.forename: Maria Helena Raposo
authors.initials: MH
authors.lastname: Fernandes
authors.affiliation: Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Brazil.
authors.forename: Flávio Augusto Cardoso
authors.initials: FA
authors.lastname: Faria
authors.affiliation: Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Brazil. Electronic address: cfsantos@fob.usp.br.
authors.forename: Carlos Ferreira
authors.initials: CF
authors.lastname: Santos
mesh_terms: D000284:Administration, Oral; D002853:Chromatography, Liquid / Q000379:methods; D006801:Humans; D010894:Piroxicam / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000032:analysis* / Q000097:blood; D012463:Saliva / Q000737:chemistry*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D010894:Piroxicam; C051024:5'-hydroxypiroxicam
keywords: 5′-Hydroxypiroxicam; LC–MS/MS; Piroxicam; Plasma; Saliva