Ciprofibrate quantification in human plasma by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry for pharmacokinetic studies


Autoria(s): MENDES, Fabiana D.; CHEN, Lu Shi; BORGES, Andre; BABADOPULOS, Tainah; ILHA, Jaime O.; ALKHARFY, Khalid M.; MENDES, Gustavo D.; NUCCI, Gilberto De
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

20/10/2012

20/10/2012

2011

Resumo

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.

Identificador

JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, v.879, n.24, p.2361-2368, 2011

1570-0232

http://producao.usp.br/handle/BDPI/28183

10.1016/j.jchromb.2011.05.055

http://dx.doi.org/10.1016/j.jchromb.2011.05.055

Idioma(s)

eng

Publicador

ELSEVIER SCIENCE BV

Relação

Journal of Chromatography B-analytical Technologies in the Biomedical and Life Sciences

Direitos

restrictedAccess

Copyright ELSEVIER SCIENCE BV

Palavras-Chave #Ciprofibrate #Healthy volunteer #Plasma #Pharmacokinetic #HPLC-MS/MS #ACID #Biochemical Research Methods #Chemistry, Analytical
Tipo

article

original article

publishedVersion