title: Budesonide quantification by HPLC coupled to atmospheric pressure photoionization (APPI) tandem mass spectrometry. Application to a comparative systemic bioavailability of two budesonide formulations in healthy volunteers.
abstract: In the present study, a novel, fast, sensitive and robust method to quantify budesonide in human plasma using 3-keto-desogestrel as the internal standard (IS) is described. The analyte and the IS were extracted from human plasma by liquid-liquid extraction (LLE) using ether. Extracted samples were analyzed by high performance liquid chromatography coupled to Atmospheric pressure photoionization tandem mass spectrometry (HPLC-APPI-MS/MS). Chromatography was performed isocratically on a C18, 5 μm analytical column. The temperature of the autosampler was kept at 6 °C and the run time was 4.00 min. A linear calibration curve over the range 7.5-1000 pg ml⁻¹ was obtained and the lowest concentration quantified was 7.5 pg ml⁻¹, demonstrating acceptable accuracy and precision. This analytical method was applied in a relative bioavailability study in order to compare a test budesonide 64 μg/dose nasal spray formulation vs. a reference 64 μg/dose nasal spray formulation (Budecort Aqua) in 48 volunteers of both sexes. The study was conducted in an open randomized two-period crossover design and with a one-week washout period. Plasma samples were obtained over a 14 h interval. Since the 90% CI for both C(max), AUC(last) and AUC(0-inf) were within the 80-125% interval proposed by the Food and Drug Administration and ANVISA, it was concluded that budesonide 64 μg/dose nasal spray was bioequivalent to Budecort Acqua® 64 μg/dose nasal spray, according to both the rate and extent of absorption.
authors.affiliation: Synchrophar Assessoria e Desenvolvimento de Projetos Clínicos S/S Ltda: 24, Cesar Bierrenbach st, Campinas, SP 13015-025, Brazil. medney@synchrophar.com
authors.forename: Ney Carter do Carmo
authors.initials: NC
authors.lastname: Borges
authors.forename: Rafael Barrientos
authors.initials: RB
authors.lastname: Astigarraga
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Sverdloff
authors.forename: Bruno Carter
authors.initials: BC
authors.lastname: Borges
authors.forename: Thaís Rodrigues
authors.initials: TR
authors.lastname: Paiva
authors.forename: Paulo Rebelo
authors.initials: PR
authors.lastname: Galvinas
authors.forename: Ronilson Agnaldo
authors.initials: RA
authors.lastname: Moreno
mesh_terms: D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D019819:Budesonide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D018592:Cross-Over Studies; D017135:Desogestrel / Q000097:blood; D004355:Drug Stability; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D059085:Nasal Sprays; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013810:Therapeutic Equivalency
chemical_list: D001993:Bronchodilator Agents; D059085:Nasal Sprays; C044815:etonogestrel; D019819:Budesonide; D017135:Desogestrel