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  • Determination of chlorpheniramine in human plasma by HPLC-ESI-MS/MS: application to a dexchlorpheniramine comparative bioavailability study.

Determination of chlorpheniramine in human plasma by HPLC-ESI-MS/MS: application to a dexchlorpheniramine comparative bioavailability study.

Biomedical chromatography : BMC (2009-11-20)
Ronilson Agnaldo Moreno, Diogo Oliveira-Silva, Carlos Eduardo Sverdloff, Bruno Carter Borges, Paulo Alexandre Rebelo Galvinas, Rafael Barrientos Astigarraga, Ney Carter Borges
ABSTRACT

In the present study a fast, sensitive and robust validated method to quantify chlorpheniramine in human plasma using brompheniramine as internal standard (IS) is described. The analyte and the IS were extracted from plasma by LLE (diethyl ether-dichloromethane, 80:20, v/v) and analyzed by HPLC-ESI-MS/MS. Chromatographic separation was performed using a gradient of methanol from 35 to 90% with 2.5 mm NH(4)OH on a Gemini Phenomenex C(8) 5 microm column (50 x 4.6 mm i.d.) in 5.0 min/run. The method fitted to a linear calibration curve (0.05-10 ng/mL, R > 0.9991). The precision (%CV) and accuracy ranged, respectively: intra-batch from 1.5 to 6.8% and 99.1 to 106.6%, and inter-batch from 2.4 to 9.0%, and 99.9 to 103.1%. The validated bioanalytical procedure was used to assess the comparative bioavailability in healthy volunteers of two dexchlorpheniramine 2.0 mg tablet formulations (test dexchlorpheniramine, Eurofarma, and reference Celestamine, Schering-Plough). 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 AUC ratios were all within the 80-125% interval proposed by ANVISA and FDA, it was concluded that test and reference formulations are bioequivalent concerning the rate and the extent of absorption.

MATERIALS
Product Number
Brand
Product Description

Dexchlorpheniramine maleate, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
S-(+)-Chlorpheniramine maleate salt
Supelco
Chlorpheniramine Maleate, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Chlorpheniramine maleate salt solution, 1.0 mg/mL in methanol (as free base), ampule of 1 mL, certified reference material, Cerilliant®
Chlorphenamine maleate, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
(±)-Chlorpheniramine maleate salt, ≥99% (perchloric acid titration)