Quantification of piroxicam and 5 '-hydroxypiroxicam in human plasma and saliva using liquid chromatography-tandem mass spectrometry following oral administration

Author(s)

Calvo, Adriana Maria ; Santos, Gabriel Mulinari ; Dionisio, Thiago Jose ; Marques, Maria Paula ; Brozoski, Daniel Thomas ; Lanchote, Vera Lucia ; Raposo Fernandes, Maria Helena ; Cardoso Faria, Flavio Augusto ; Santos, Carlos Ferreira

• Document type: Journal article
• Source: Journal of Pharmaceutical and Biomedical Analysis; v. 120, p. 9-pg., 2016-02-20.

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 1 mL/min. The run time was 4 min. Volunteers had saliva and blood sampled before, 1, 2, 3, 4, 5, 6, 8, 11, 24, 48 and 72 h after taking a 20 mg oral dose of piroxicam. The pharmacokinetic parameters of piroxicam in plasma samples were as follows: AUC(0-72) (64819 h ng/mL), predicted clearance (0.2 L/h), distribution volume (14.8 L), elimination half-life (50.7 h) and saliva/plasma concentration ratio (0.003). The"estimation of all pharmacokinetic parameters for 5'-hydroxypiroxicam would require collections beyond 72 h; however, it was possible to quantify the mean maximum concentration (133 ng/mL), time to peak concentration (53.6 h), mean AUC(0-72) (6213 h ng/mL), predicted clearance (110.31.1h) and saliva/plasma concentration ratio (0.04). The developed methods proved effective and sensitive for determining the lower quantification limit of piroxicam in plasma (6.1 ng/mL) and saliva (0.15 ng/mL) and of 5'-hydroxypiroxicam in plasma (1.2 ng/mL) and saliva (0.15 ng/mL). (C) 2015 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 14/17803-1 - Influence of genotype of cytochrome P450 (CYP2C9) on the clinical efficacy and pharmacokinetics of Piroxicam after lower third molar surgery
• Grantee: Carlos Ferreira dos Santos
• Support Opportunities: Regular Research Grants
• FAPESP's process: 09/17851-8 - Influence of cytochrome P450 (CYP2C9) genotype on the clinical efficacy and pharmacokinetics of piroxicam after lower third molar surgery
• Grantee: Adriana Maria Calvo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/10198-8 - Study of the pharmacogenetics of the cytochrome p450 and pharmacokinetics of piroxicam in saliva samples by mass spectrometry
• Grantee: Gabriel Mulinari dos Santos
• Support Opportunities: Scholarships in Brazil - Scientific Initiation