LC-ICP-MS for Nonmetal Selective Detection of Pharmaceuticals

John   E.   Carr; Adam   E.   Dill; Kaho      Kwok; Jon   W.   Carnahan; Gregory   K.   Webster

Abstract

Liquid chromatography (LC) remains the technique of choice for analytical separations of pharmaceutical compounds. Still today, new detector and column technologies are taking liquid chromatography to lower quantitation levels and improved selectivity. While known throughout the chemical, environmental and pharmaceutical industries as the stalwart technique for metals analysis, recent trade publications substantiate inductively coupled plasma mass spectrometry (ICP-MS) is making significant inroads in nonmetal testing for pharmaceutical analysis as well. Coupling ICPMS to liquid chromatography is not only providing new and enhanced sensitivity and selectivity for pharmaceutical separations but also eliminates the need for internal standards for each analyte in order to obtain accurate quantitative results. Both inductively coupled plasma atomic emission spectrometry (ICP-AES) and inductively coupled plasma mass spectrometry rely on sample decomposition to convert analytes to atomic forms; such drawbacks can be minimized or eliminated. Nonmetal sensitivity and selectivity for pharmaceutical compounds is of particular interest for genotoxic impurity determinations and difficult clinical matrices. The performance of coupling LC systems to ICP-MS will be reviewed; the separation of several pharmaceutical compounds containing sulfur, phosphorous, chlorine and fluorine will be presented to illustrate the capabilities of this technique and point to future directions for pharmaceutical analysis. The effects on sensitivity of various mobile phases and gradients, and the correlation between this study and earlier studies with direct sample nebulization will be discussed.

Keywords: LC, ICP-AES, ICP-MS, Nonmetals analysis, Genotoxic impurity detection

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