Clinical pharmacokinetics and bioequivalence of nimesulide dispersible tablets by LC-MS/MS method

Objective:To establish an LC-MS/MS method for the determination of nimesulide in human plasma,used for the study of the clinical pharmocokinetics and bioequivalence of nimesulide dispersible tablets.Methods:In a randomized two-way self-crossover study,20 healthy male volunteers were divided into two groups,and were administered respectively either with a single oral dose of test or reference preparations containing 100 mg of nimesulide.The blood samples were collected at predetermined time intervals within 24 hours.The plasma concentration of nimesulide was determined by LC-MS/MS.The chromatographic separation was performed on an Agilent TC-C18(250 mm ×4.6 mm,5 μm)column with a mobile phase consisting of methanol and water solvent with 0.1% formic acid(82∶ 18,v/v).The analytes were detected by multiple reaction monitoring of the +ions with transitions of m/z 309.1→m/z 153.9 and m/z 237.1→m/z 194.0 for nimesulide and carbamazepine,respectively.The pharmacokinetic parameters were estimated by DAS 2.1.Results:The peak areas and concentrations showed good correlation in the range of 0.075-12 μg·mL-1with a LOQ of 0.075 μg·mL-1 for quantitation of nimesulide in human plasma.The intra-and inter-batch precision RSDs were less than 15%.The pharmacokinetic parameters of the test and reference tablets were as follows:Tmax(3.0±0.7)and(3.5±1.0)h,Cmax(4.863±1.194)and(4.657±1.038)μg·mL-1,t1/2(3.2±1.0)and(3.3±1.1)h,AUC0-24 h(32.35±12.50)and(32.32±11.69)h·μg·mL-1,respectively.The relative bioavailability F was(105.2%±35.0)%.Conclusion:The method is accurate,sensitive,reliable and suitable for the pharmacokinetic study of nimesulide.The two preparations are bioequivalent.