Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/942
Type: Artigo de periódico
Title: Ciprofibrate quantification in human plasma by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry for pharmacokinetic studies
Author: MENDES, Fabiana D.
CHEN, Lu Shi
BORGES, Andre
BABADOPULOS, Tainah
ILHA, Jaime O.
ALKHARFY, Khalid M.
MENDES, Gustavo D.
NUCCI, Gilberto De
Abstract: A rapid, sensitive and specific method for quantifying ciprofibrate in human plasma using bezafibrate as the internal standard (IS) is described. The sample was acidified prior extraction with formic acid (88%). The analyte and the IS were extracted from plasma by liquid-liquid extraction using an organic solvent (diethyl ether/dichloromethane 70/30 (v/v)). The extracts were analyzed by high performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-MS/MS). Chromatography was performed using Genesis C18 4 mu m analytical column (4.6 x 150 mm i.d.) and a mobile phase consisting of acetonitrile/water (70/30, v/v) and 1 mM acetic acid. The method had a chromatographic run time of 3.4 min and a linear calibration curve over the range 0.1-60 mu g/mL (r > 0.99). The limit of quantification was 0.1 mu g/mL. The intra- and interday accuracy and precision values of the assay were less than 13.5%. The stability tests indicated no significant degradation. The recovery of ciprofibrate was 81.2%, 73.3% and 76.2% for the 0.3, 5.0 and 48.0 ng/mL standard concentrations, respectively. For ciprofibrate, the optimized parameters of the declustering potential, collision energy and collision exit potential were -51 V, -16 eV and -5 V, respectively. The method was also validated without the use of the internal standard. This HPLC-MS/MS procedure was used to assess the bioequivalence of two ciprofibrate 100 mg tablet formulations in healthy volunteers of both sexes. The following pharmacokinetic parameters were obtained from the ciprofibrate plasma concentration vs. time curves: AUC(last), AUC(0-168 h), C(max) and T(max). The geometric mean with corresponding 90% confidence interval (CI) for test/reference percent ratios were 93.80% (90% CI = 88.16-99.79%) for C(max), 98.31% (90% CI = 94.91-101.83%) for AUC(last) and 97.67% (90% CI = 94.45-101.01%) for AUC(0-168 h). Since the 90% Cl for AUC(last), AUC(0-168 h) and C(max) ratios were within the 80-125% interval proposed by the US FDA, it was concluded that ciprofibrate (Lipless (R) 100 mg tablet) formulation manufactured by Biolab Sanus Farmaceutica Ltda. is bioequivalent to the Oroxadin (R) (100 mg tablet) formulation for both the rate and the extent of absorption. (C) 2011 Published by Elsevier B.V.
Subject: Ciprofibrate
Healthy volunteer
Plasma
Pharmacokinetic
HPLC-MS/MS
Country: Holanda
Editor: ELSEVIER SCIENCE BV
Rights: fechado
Identifier DOI: 10.1016/j.jchromb.2011.05.055
Address: http://dx.doi.org/10.1016/j.jchromb.2011.05.055
http://apps.isiknowledge.com/InboundService.do?Func=Frame&product=WOS&action=retrieve&SrcApp=EndNote&UT=000294239800001&Init=Yes&SrcAuth=ResearchSoft&mode=FullRecord
Date Issue: 2011
Appears in Collections:FCM - Artigos e Materiais de Revistas Científicas

Files in This Item:
File Description SizeFormat 
art_MENDES_Ciprofibrate_quantification_in_human_plasma_by_high-performance_2011.pdfpublished version774.02 kBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.