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

Abstract

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°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 [Tmax 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 [T1/2 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 (Cmax 4.6 ± 2.5 ug/mL for naproxen alone and 2.04 ± 0.78* μg/mL, p = 0.038). The association of naproxen with esomeprazole showed increased values of AUC0-t [82.06* h*μg/mL (interquartile range, 51.90–157.00) with esomeprazole and 2.97 h*μg/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* μg/h (interquartile range, 0.005–0.01) with esomeprazole and 7.29 μg/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.

Liquid Chromatography-Tandem Mass Spectrometry Method for Detection and Quantification of Meloxicam and 5′-Carboxymeloxicam in Oral Fluid Samples

“…The validation parameters were evaluated with freshly prepared calibration curves. Stability was accepted when the deviation from the nominal value was equal to or less than ±15% [ 21 , 27 , 28 , 31 ].…”

“…For the PGE 2 calibration curve, the concentrations used were: 2500, 1250, 625, 312.5, 156.2, 78.1, 39.1, 19.5, 9.8 and 2.4 ng/mL. All polypropylene tubes were stored at −20 °C until use [ 21 , 27 , 28 , 31 ].…”

“…Through the concentrations obtained experimentally, the pharmacokinetic parameters were determined using the Phoenix WinNonlin Software (version 8.1) (Certara L.P, Princeton, NJ, USA.) with the non-compartmental model with elimination [ 27 , 28 , 31 ].…”

“…Due to the numerous sample collections required for a pharmacokinetic study (up to 96 h), the use of alternative samples, such as oral fluid, has shown promise, even for NSAIDs [ 26 , 27 , 28 , 29 , 30 , 31 ]. Some analytical methodologies were developed in human plasma for the detection of meloxicam after the ingestion of a 7.5 mg tablet [ 32 ], 15 mg tablet [ 33 ] and transdermal application [ 34 ], but studies about the detection and determination of this drug in oral fluid samples have not been reported.…”

“…When compared to other methodologies, this device has advantages due to time savings. The various stages can be considered harmful to the results given the prolonged extraction and drying time, such as the non-ecological use of plastic material [ 26 , 28 , 29 , 30 , 31 ].…”