Simultaneous separation of naproxen and 6-O-desmethylnaproxen metabolite in saliva samples by liquid chromatography-tandem mass spectrometry: Pharmacokinetic study of naproxen alone and associated with esomeprazol-Results

Autor(es)

Oliveira, Gabriela Moraes ; Dionisio, Thiago Jose ; Del Hierro Polanco, Nelson Leonel ; Siqueira-Sandrin, Viviane Silva ; Cardoso Faria, Flavio Augusto ; Santos, Carlos Ferreira ; Calvo, Adriana Maria

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 17, n. 12, p. 11-pg., 2022-12-01.

Resumo

After performing liquid-liquid extraction with ethyl acetate and HCl, samples from 12 volunteers who performed sequential collections after taking a tablet of naproxen alone (n = 6) or associated with esomeprazole (n = 6) were analyzed in a triple quadrupole mass spectrometer 8040 LC MS/MS Shimadzu. Separation of naproxen and its main metabolite 6-O-desmethylnaproxen was performed in a Shim-Pack XR-ODS 75Lx2.0 column and C18 pre-column at 40 degrees C using a mixture of methanol and ammonium acetate 10 mM (70:30, v/v) with an injection rate of 0.3 ml/min. The total analytical run time for each sample was 5 min. The association of naproxen with esomeprazole take considerably longer time to reach the maximum concentration [T-max 0.17 h (interquartile range, 0.13-1.95) for naproxen alone and 13.18*h (interquartile range, 10.12-27.15) for naproxen with esomeprazole, p = 0.002], also to be eliminated [T-1/2 0.12 h (interquartile range, 0.09-1.35) for naproxen alone and 9.16*h (interquartile range, 7.16-41.40) for naproxen with esomeprazole, p = 0.002] and lower maximum concentrations (C-max 4.6 +/- 2.5 ug/mL for naproxen alone and 2.04 +/- 0.78* mu g/mL, p = 0.038). The association of naproxen with esomeprazole showed increased values of AUC(0-t) [82.06* h*mu g/mL (interquartile range, 51.90-157.00) with esomeprazole and 2.97 h*mu g/mL (interquartile range, 1.82-7.84) naproxen alone, p = 0.002] in drug concentrations in relation to the naproxen tablet alone, probably, such differences are due to the delay in the absorption of naproxen when it is associated with the drug proton pump inhibitor, esomeprazole. As well as reduced values of full clearance when naproxen is combined with esomeprazole (0.07* mu g/h (interquartile range, 0.005-0.01) with esomeprazole and 7.29 mu g/h (interquartile range, 3.17-16.23) in naproxen alone, p = 0.002). Both naproxen and 6-O-desmethylnaproxen in saliva samples can be effectively quantified using LC-MS/MS, this methodology proved to be rapid, sensitive, accurate and selective for each drug and allows for the analysis of their pharmacokinetic parameters, in both situations. (AU)

• Processo FAPESP: 20/04730-7 - Análise de diferentes métodos de extração de fármacos em amostras de saliva para ensaios em LC MS/MS
• Beneficiário: Viviane da Silva Siqueira Sandrin
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 20/04734-2 - Farmacocinética do naproxeno, celecoxib e meloxicam e validação da metodologia de extração em amostras de saliva por LC MS/MS
• Beneficiário: Nelson Leonel Del Hierro Polanco
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 17/12725-0 - Modelo de farmacocinética/farmacodinâmica (PK/PD) na influência do polimorfismo genético do P450 (CYP2C9) de anti-inflamatórios não esteroidais e metabólitos principais a partir de amostras de saliva por LCMS/MS e seu papel na personalização da prescrição
• Beneficiário: Adriana Maria Calvo
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores