Design and evaluation of a multi-detection system composed of ultraviolet, evaporative light scattering and inductively coupled plasma mass spectrometry detection for the analysis of pharmaceuticals by liquid chromatography

Reversed-phase liquid chromatography was coupled to a multi-detection system composed of ultraviolet (UV) detection, evaporative laser scattering detection (ELSD) and inductively coupled plasma mass spectrometry (ICP-MS). By applying the principle of post-column solvent compensation, the organic modifier content was kept constant in ELSD and ICP-MS under gradient elution. Chlorine (35Cl), bromine (79Br and 81Br) and sulfur (34S) were monitored in several pharmaceutical compounds. The limit of quantitation (LOQ) was 80 ng/mL for chlorine (chlorpropamide) and 2 ng/mL for bromine (bromazepam). Calibration graphs were linear from 1.0 μg/mL to 100 μg/mL for chlorpropamide (r2 0.990) and from 10 ng/mL to 500 ng/mL for bromazepam (r2 0.996). The low LOQ value for bromine allows to quantify bromine in pharmaceutical samples below the 0.05% level of the active pharmaceutical ingredient.