Ticlopidine quantification in human plasma by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry. Application to bioequivalence study.
A rapid, sensitive and specific method to quantify ticlopidine in human plasma using clopidogrel as the internal standard (IS) is described. The analyte and the IS were extracted from acidified plasma by liquid-liquid extraction using diethyl ether-hexane (80 : 20, v/v). The extracts were analyzed by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry (HPLC/MS/MS). Chromatography was performed isocratically on a Jones Genesis C(8) 4 microm analytical column (150 x 4.1 mm i.d.). The method had a chromatographic run time of 3.0 min and a linear calibration curve over the range 1.0-1000 ng ml(-1) (r(2) > 0.999427). The limit of quantification was 1.0 ng ml(-1). This HPLC/MS/MS procedure was used to assess the bioequivalence of two ticlopidine 250 mg tablet formulations (ticlopidine test formulation from Apotex do Brasil, Brazil, and Ticlid from Sanofi-Synthelabo, standard reference formulation). A single 250 mg dose of each formulation was administered to healthy volunteers. The study was conducted using an open, randomized, two-period crossover design with a 2 week washout interval. Since the 90% confidence interval for C(max) and area under the curve ratios were all inside the 80-125% interval proposed by the US Food and Drug Administration, it was concluded that ticlopidine formulation from Apotex do Brasil is bioequivalent to Ticlid formulation with respect to both the rate and the extent of absorption.
Borges
Ney Carter do Carmo
NC
Department of Pharmacology, State University of Campinas, P.O. Box 6111 Campinas, SP, Brazil.
Mendes
Gustavo Duarte
GD
Borges
André
A
Oliveira
Sandro Evandir de
SE
Barrientos-Astigarraga
Rafael Eliseo
RE
De Nucci
Gilberto
G
D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000097:blood; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013810:Therapeutic Equivalency; D013988:Ticlopidine / Q000097:blood*
D010975:Platelet Aggregation Inhibitors; D013988:Ticlopidine