Synthesis and Characterization of Maillard Reaction Products of Salbutamol and Terbutaline with Lactose and Development and Validation of an LC Method for the Determination of Salbutamol and Terbutaline in the Presence of These Impurities.

Abstract

Being secondary amines, both salbutamol (SLB) and terbutaline (TRB) react by Maillard reaction (MR) with lactose, which is added as an inactive ingredient in tablets. The Amadori rearrangement products were synthesized, isolated, and characterized by mass spectrometry. In addition, a simple, selective, and precise reversed-phase liquid chromatography (LC) method was developed and validated for the determination of SLB and TRB in tablets, each in the presence of its MR impurity. The chromatographic separation was performed on a Symmetry(®) Waters C18 column (150 mm × 4.6 mm, 5 μm) using a mobile phase consisting of 0.5% aqueous phosphoric acid to acetonitrile (90:10, v/v) at a flow rate of 0.7 mL minute(-1). Quantitation was achieved using UV detection at 230 nm. Linearity, accuracy, and precision were found to be acceptable for the determination of SLB and TRB in the concentration range of 0.2-60 and 0.5-80 μg mL(-1), respectively. The proposed method was successfully applied to the determination of SLB and TRB in bulk and in their tablets.