Quantification of nimesulide in human plasma by high-performance liquid chromatography/tandem mass spectrometry. Application to bioequivalence studies.
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.
Barrientos-Astigarraga
R E
RE
Cartesius Analytical Unit, Department of Pharmacology, Institute of Biomedical Sciences, Av. Prof. Lineu Prestes 1524, São Paulo, SP, 05508-900, Brazil.
Vannuchi
Y B
YB
Sucupira
M
M
Moreno
R A
RA
Muscará
M N
MN
De Nucci
G
G
D000293:Adolescent; D000328:Adult; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D004986:Ether; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008752:Methylene Chloride; D008875:Middle Aged; D011786:Quality Control; D012680:Sensitivity and Specificity; D013449:Sulfonamides / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D013810:Therapeutic Equivalency
D013449:Sulfonamides; D004986:Ether; D008752:Methylene Chloride; C012655:nimesulide