Quantification of nimesulide in human plasma by high-performance liquid chromatography/tandem mass spectrometry. Application to bioequivalence studies

✍ Scribed by Rafael Eliseo Barrientos-Astigarraga; Yuri Borges Vannuchi; Mauro Sucupira; Ronilson Agnaldo Moreno; Marcelo Nicolás Muscará; Gilberto De Nucci

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 152 KB
• Volume: 36
• Category: Article
• ISSN: 1076-5174
• DOI: 10.1002/jms.232

✦ Synopsis

Abstract

A method based on liquid chromatography with negative ion electrospray ionization and tandem mass spectrometry is described for the determination of nimesulide in human plasma. Liquid–liquid extraction using a mixture of diethyl ether and dichloromethane was employed and celecoxib was used as an internal standard. The chromatographic run time was 4.5 min and the weighted (1/x) calibration curve was linear in the range 10.0–2000 ng ml^−1^. The limit of quantification was 10 ng ml^−1^, the intra‐batch precision was 6.3, 2.1 and 2.1% and the intra‐batch accuracy was 3.2, 0.3 and 0.1% for 30, 300 and 1200 ng ml^−1^ respectively. The inter‐batch precision was 2.3, 2.8 and 2.7% and the accuracy was 3.3, 0.3 and 0.1% for 30, 300 and 1200 ng ml^−1^ respectively. This method was employed in a bioequivalence study of one nimesulide drop formulation (nimesulide 50 mg ml^−1^ drop, Medley S/A Indústria Farmacêutica, Brazil) against one standard nimesulide drop formulation (Nisulid, 50 mg ml^−1^ drop, Astra Médica, Brazil). Twenty‐four healthy volunteers (both sexes) took part in the study and received a single oral dose of nimesulide (100 mg, equivalent to 2 ml of either formulation) in an open, randomized, two‐period crossover way, with a 2‐week washout interval between periods. The 90% confidence interval (CI) for geometric mean ratios between nimesulide and Nisulid were 93.1–109.6% for C~max~, 87.7–99.8% for AUC~last~ and 88.1–99.7% for AUC~0–∞~. Since the 90% CI for the above‐mentioned parameters were included in the 80–125% interval proposed by the US Food and Drug Administration, the two formulations were considered bioequivalent in terms of both rate and extent of absorption. Copyright © 2001 John Wiley & Sons, Ltd.