Premium
Determination of 21‐hydroxydeflazacort in human plasma by high‐performance liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry. Application to bioequivalence study
Author(s) -
Ifa Demian R.,
Moraes Maria E.,
Moraes Manuel O.,
Santagada Vincenzo,
Caliendo Giuseppe,
Nucci Gilberto de
Publication year - 2000
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/(sici)1096-9888(200003)35:3<440::aid-jms955>3.0.co;2-8
Subject(s) - chemistry , chromatography , atmospheric pressure chemical ionization , mass spectrometry , chemical ionization , bioequivalence , tandem mass spectrometry , direct electron ionization liquid chromatography–mass spectrometry interface , liquid chromatography–mass spectrometry , tandem , analytical chemistry (journal) , atmospheric pressure , human plasma , ionization , organic chemistry , ion , pharmacokinetics , medicine , materials science , oceanography , composite material , geology
A liquid chromatographic atmospheric pressure chemical ionization tandem mass spectrometric method is described for the determination of 21‐hydroxydeflazacort in human plasma using dexamethasone 21‐acetate as an internal standard. The procedure requires a single diethyl ether extraction. After evaporation of the solvent under a nitrogen flow, the analytes are reconstituted in the mobile phase, chromatographed on a C 18 reversed‐phase column and analyzed by mass spectrometry via a heated nebulizer interface where they are detected by multiple reaction monitoring. The method has a chromatographic run time of less than 5 min and a linear calibration curve with a range of 1–400 ng ml −1 ( r > 0.999). The between‐run precision, based on the relative standard deviation for replicate quality controls, was ≤5.5% (10 ng ml −1 ), 1.0% (50 ng ml −1 ) and 2.7% (200 ng ml −1 ). The between‐run accuracy was ±7.1, 3.8 and 4.8% for the above concentrations, respectively. This method was employed in a bioequivalence study of two DFZ tablet formulations (Denacen from Marjan Industria e Comercio, Brazil, as a test formulation, and Calcort from Merrell Lepetit, Brazil, as a reference formulation) in 24 healthy volunteers of both sexes who received a single 30 mg dose of each formulation. The study was conducted using an open, randomized, two‐period crossover design with a 7‐day washout interval. The 90% confidence interval (CI) of the individual geometric mean ratio for Denacen/Calcort was 89.8–109.5% for area under the curve AUC (0–24 h) and 80.7–98.5% for C max . Since both the 90% CI for AUC (0–24 h) and C max were included in the 80–125% interval proposed by the US Food and Drug Administration, Denacen was considered bioequivalent to Calcort according to both the rate and extent of absorption. Copyright © 2000 John Wiley & Sons, Ltd.