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

• Published in: Biomedical chromatography 2010-11, Vol.24 (11), p.1220-1227
• Main Authors: Moreira, Roberto F., Salvadori, Myriam C., Azevedo, Cristina P., Oliveira-Silva, Diogo, Borges, Diego C., Moreno, Ronílson A., Sverdloff, Carlos E., Borges, Ney C.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; bioequivalence; Biological Availability; Chromatography, Liquid - methods; Female; HPLC; Humans; Male; mass spectrometry; Middle Aged; ondansetron; Ondansetron - blood; Ondansetron - pharmacokinetics; pharmacokinetics; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization - methods; Tandem Mass Spectrometry - methods; Young Adult
• ISSN: 0269-3879; 1099-0801
• DOI: 10.1002/bmc.1431

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 Cmax and 93.11% (83.01–104.43%) for AUC0–t. Based on the 90% confidence interval of the individual ratios (test formulation/reference formulation) for Cmax and AUC0‐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. Copyright © 2010 John Wiley & Sons, Ltd.