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.
Department of Medical Clinic, State University of Campinas, Campinas/SP, Brazil.
Roberto F
RF
Moreira
Myriam C
MC
Salvadori
Cristina P
CP
Azevedo
Diogo
D
Oliveira-Silva
Diego C
DC
Borges
Ronílson A
RA
Moreno
Carlos E
CE
Sverdloff
Ney C
NC
Borges
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