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

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 x ml(-1). The limit of quantification was 10 ng x 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 x 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 x ml(-1) respectively. This method was employed in a bioequivalence study of one nimesulide drop formulation (nimesulide 50 mg x ml(-1) drop, Medley S/A Indústria Farmacêutica, Brazil) against one standard nimesulide drop formulation (Nisulid, 50 mg x 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-infinity). 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.

Human metabolism of [14C]indisulam following i.v. infusion in cancer patients

“…Most of the fragmentations presented involve the loss of m/z 64 (SO 2 ) from the structure without loss of the distal amine. This extraction of the SO 2 moiety from sulphonamide structures has been observed earlier, although the exact mechanism remains unclear [17][18][19].…”

LC-MS/MS determination of 4-hydroxynimesulide, an active metabolite of nimesulide and application to bioequivalence study in Indian subjects

“…1,2 It is a selective inhibitor of cyclo-oxygenase-2 (COX-2) and effectively provides relief from a wide variety of pain (like analgesic and antipyretic) and inflammatory conditions (like anti-inflammatory). [3][4][5][6] Apart from this potent anti-inflammatory effect, it has been stated that longterm administration of NSD caused hepatotoxicity 7,8 and gastrointestinal toxicity 9 in human being. NSD has various mechanisms of action in its pharmacological activities.…”

“…Also, the bioequivalence studies were performed for only NSD, but not for M1 in human plasma. 4 Another HPLC method was reported by Carini et al 19 for the quantitative determination of the main urinary metabolites of NSD in urine with lower limit of quantitation (LLOQ) of 25 ng/mL and a very long chromatographic run time. Also it has a complicated time-consuming extraction technique with too much of solvents.…”

Fluorescence Spectrometric Determination of Drugs Containing -Methylene Sulfone/Sulfonamide Functional Groups UsingN1-Methylnicotinamide Chloride as a Fluorogenic Agent

“…Electrochemical methods involve flow amperometry [45] and adsorptive stripping voltammetry [46]. Separation methods involve HPLC [47, 48] and HPLC-MS/MS [49]. …”