Determination of halogens in organic compounds by high resolution inductively coupled plasma mass spectrometry (HR-ICP-MS)

Abstract

The feasibility of the determination of sub ppm to percentage levels of halogen elements (fluorine, chlorine, bromine, and iodine) in solid organic compounds and drug substances by double focusing sector field high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS) was investigated. Samples were dissolved in appropriate solvents and then diluted in either deionized water or 5% (v/v) ammonium hydroxide. By applying medium or high resolution, the background counts can be lowered by up to five orders of magnitude compared to conventional quadrupole ICP-MS systems. The signal sensitivities and memory effects of all four elements in different solvents were compared and assessed. The methods were applied to the determination of sub ppm to percentage levels of F, Cl, Br and I in a series of organic compounds and Merck drug substances. The results were found to be in excellent-to-reasonable agreement with the known or theoretical values of these compounds or drug substances. The limit of detection in solution for F was estimated to be 5 µg ml⁻¹ (medium resolution), and for Cl, Br and I was 3 (high resolution), 0.08 (high resolution) and 0.03 (high resolution) ng ml⁻¹, respectively.