THE SOLVENT OPTIMIZATION IN METOPROLOL DERIVATIZATION REACTION WITH 1-FLUORO-2,4-DINITROBENZENE

Abstract

Metoprolol, or 1-[4-(2-Methoxyethyl)phenoxy]-3-[(1-methylethyl)amino]-2-propanol, is a β1adrenergic

receptor antagonist that is often used to treat cardiovascular disorders such as
hypertension, arrhythmia, and heart failure. Metoprolol has an A value of
1%
1cm
= 52a in

acid
solution at a wavelength of 274 nm, where the molar absorptivity value (Ԑ) is 1390.48 L/(mol .
cm) so that metoprolol gives weak absorption in the UV region (Ԑ ~ 1000 L/(mol . cm)). This
study aims to optimize the solvent in the derivatization reaction of metoprolol with 1-fluoro-2,4dinitrobenzene

(FDNB). Under optimum conditions, the metoprolol reaction should form a
derivatization product with FDNB. Metoprolol derivatization reaction in methanol solvent is
optimal at pH 10.0 in borate buffer, with a warm-up at room temperature for 80 minutes.
Analysis of metoprolol by High Performance Liquid Chromatography (HPLC) using a
Chromolith RP-18e column (100 mm x 4.6 mm; 2 µm) and phase acetonitrile: buffer acetate (0.2
M, pH 3.0) = 70:30 with a flow rate of 1.0 ml/min. Separation of metoprolol-DNB occurs at a
time retention of 7,856 minutes, with an analysis time of 10 minutes. Reaction-derivatization of
metoprolol in methanol solvent; the optimum condition was pH 10.0. It was concluded that
metoprolol in methanol solvent was more effective because the derivatization reaction with
FDNB did not require heating. Optimizing the metoprolol content determination method using
the FDNB solution derivatizer in acetonitrile showed that the optimal mobile phase was a
mixture of acetonitrile and 0.2 M acetate buffer (30:70, pH 3.0), with a flow rate of 1.0
mL/minute.

Keywords: FDNB, HPLC, metoprolol, optimization