Capillary electrophoresis -- high resolution inductively coupled plasma mass spectrometry: elemental speciation and applications in pharmaceutical process research

Abstract

The high efficiency of capillary electrophoresis (CE) was combined with the element specificity and low detection limits of high resolution inductively coupled plasma mass spectrometry (HR-ICP MS) for rapid elemental speciation. A novel sheath flow interface coupled to a PFA Teflon micro-flow concentric nebulizer was developed to provide an efficient method for interfacing capillary electrophoresis with the inductively coupled plasma. The sheath interface provides control over the nebulizer induced laminar flow in the separation capillary allowing the tradeoff between separation efficiency and analysis time to be selected. In chapter 3, this CE-HR-ICP-MS system was used to study various hydration/hydrolysis processes of hexachloro complexes of Rh in aqueous solutions. The migration speed of various mixed aquo/chloro rhodium species through the capillary depends on the charges they carry, which is dictated by the solution pH as well as their aging period in the solution. Several Rh species were tentatively identified according to their relative mobilities and their equilibrium distributions were quantified using peak area calculation in the experiments. In chapter 4, to meet the need of speciation analysis for applications in pharmaceutical process research, a non-aqueous CE with HR-ICP-MS detection method was developed. The novel sheath interface between the CE and ICP-MS enabled the use of CE with up to 100% organic electrolyte without organic loading in the plasma. Two unique aspects of non-aqueous CE, non-aqueous CE with wide-bore capillaries and influence of organic solvent on the CE separation selectivity were discussed. Information on chemical speciation is much needed in mechanistic and kinetic studies on catalyst formation processes in pharmaceutical research. In chapter 5, non-aqueous CE-ICP-MS speciation analysis was applied to the identification and quantification of various rhodium species involved in a ligand exchange process leading to formation of catalyst dirhodium(II) tetrakis[methyl 2-oxopyrrolidin-5(S)-carboxylate]. A variety of reaction intermediates were identified and quantified along the pathway to formation of the desired product. This has provided new insights into the mechanism and kinetics of the reaction. In chapter 6, 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 HR-ICP-MS was investigated. In chapter 7, the application of HR-ICP-MS for the determination of isotopic composition of enriched stable isotope calcium samples is described. The interferences from 40Ar isotope at the calcium mass 40 are greatly minimized by operating the ICP-MS in the cool plasma mode. The rest polyatomic ions are overcome by high resolution mode of the ICP-MS.%%%%