Simultaneous separation of naproxen and 6-O-desmethylnaproxen metabolite in saliva samples by LC MS / MS: PK study of naproxen associated or not with esomeprazole

Published: 17-07-2020| Version 1 | DOI: 10.17632/zwsg6z5p8d.1
Thiago Dionisio,
Marina Morettin,
Flavio A. C. Faria,
Carlos F. Santos,
Adriana Calvo


Naproxen is a well-known and widely used non-steroidal anti-inflammatory drug (NSAID) for the control of postoperative inflammatory signs and symptoms in dentistry. Its association with esomeprazole has been widely studied nowadays and bringing good results also for the control of acute pain, even with the delayed absorption of naproxen due to the presence of esomeprazole. To further understand the absorption, distribution and metabolization of this drug alone or in combination with esomeprazole, we will analyze the pharmacokinetic parameters of naproxen and its major metabolite, 6-O-desmethylnaproxen in saliva samples. For that, a rapid, sensitive and selective liquid chromatography-tandem mass spectrometric method for simultaneous determination of naproxen and 6-O-desmethilnaproxen in saliva will be developed and validated. Sequential saliva samples from 6 patients will be analyzed before, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6 8, 11, 24, 48, 72 and 96 h after ingestion of one naproxen tablet (500 mg) and esomeprazole-associated naproxen tablet (500 + 20 mg), at two different times. After liquid-liquid extraction with ethyl acetate and HCl, the samples will be analyzed by 8040 Triple Quadrupole Mass Spectrometer (MS / MS) (Shimadzu, Kyoto, Japan). Separation of naproxen and its major metabolic will be performed by Shim-Pack XR-ODS 75Lx2.0 column and C18 pre-column (Shimadzu, Kyoto, Japan) at 40 ° C using as mobile phase a mixture of methanol and 10 mM ammonium acetate (70:30, v / v) with injection flow of 0.3 mL / min. The total analytical run time will be 5 minutes. The naproxen and its metabolite detection and quantification will be validated, which will allow to know the pharmacokinetics of this drug, and thus contribute to its proper prescription for the different medical and dental interventions that cause acute pain.