Development and validation of a rapid and sensitive LC-ESI-MS/MS method for ondansetron quantification in human plasma and its application in comparative bioavailability study.
The validation of a high throughput and specific method using a high-performance liquid chromatography coupled to electrospray (ES+) ionization tandem triple quadrupole mass spectrometric (LC-ESI-MS/MS) method for ondansetron quantification in human plasma is described. Human plasma samples were extracted by liquid-liquid extraction (LLE) using methyl tert-butyl ether and analyzed by LC-ESI-MS/MS. The limit of quantification was 0.2 ng/mL and the method was linear in the range 0.2-60 ng/mL. The intra-assay precisions ranged from 1.6 to 7.7%, while inter-assay precisions ranged from 2.1 to 5.1%. The intra-assay accuracies ranged from 97.5 to 108.2%, and the inter-assay accuracies ranged from 97.3 to 107.0%. The analytical method was applied to evaluate the relative bioavailability of two pharmaceutical formulations containing 8 mg of ondansetron each in 25 healthy volunteers using a randomized, two-period crossover design. The geometric mean and respective 90% confidence interval (CI) of ondansetron test/reference percent ratios were 90.15% (81.74-99.44%) for C(max) and 93.11% (83.01-104.43%) for AUC(₀-t). Based on the 90% confidence interval of the individual ratios (test formulation/reference formulation) for C(max) and AUC(₀-inf), it was concluded that the test formulation is bioequivalent to the reference one with respect to the rate and extent of absorption of ondansetron.
Moreira
Roberto F
RF
Department of Medical Clinic, State University of Campinas, Campinas/SP, Brazil.
Salvadori
Myriam C
MC
Azevedo
Cristina P
CP
Oliveira-Silva
Diogo
D
Borges
Diego C
DC
Moreno
Ronílson A
RA
Sverdloff
Carlos E
CE
Borges
Ney C
NC
D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017294:Ondansetron / Q000097:blood* / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult
D017294:Ondansetron