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Direct analysis of liquid drugs by inductively coupled plasma mass spectrometry using aerosol dilution

Abstract

In this work, a method for the direct analysis of liquid drug samples by inductively coupled plasma mass spectromety (ICP-MS) with aerosol dilution was proposed. Multivariate studies were executed for optimization of ICP-MS parameters (sample depth, aerosol dilution gas-flow and He gas-flow) using a representative diluted drug sample aiming appropriate plasma robustness parameters (140Ce2+/140Ce+ and 140Ce16O+/140Ce+ ratios), as well as sensitivity for Ag, As, Au, Ba, Cd, Co, Cr, Cu, Hg, Ir, Li, Mo, Ni, Os, Pb, Pd, Pt, Rh, Ru, Sb, Se, Sn, Tl and V, the elemental impurities in USP Chapter 232 protocol. Results showed that dilution gas had major role on doubly-charged and oxide ions formation. A robust plasma condition was achieved (i.e., 140Ce2+/140Ce+ < 0.9% and 140Ce16O+/140Ce+ < 0.3%) when 0.40 L min-1 dilution gas flow was used. The combination of collision gas and dilution gas flow rates was the key feature for minimizing (or even removing) polyatomic interferences. It was found that collision cell benefits from less sample matrix introduction provided by aerosol dilution. A validation protocol has been executed and reported for a liquid drug for hepatic disorders using the optimized procedure, and results successfully met the requirements of USP Chapter 233, wherein appropriate figures of merit (R>0.995, RSD<6.2% for precision tests, RSD<14% for intermediary precision test, and 88-125% recoveries for 50-fold diluted spiked sample with different J concentrations) were obtained. This study provided useful information about the benefits of aerosol dilution and demonstrates that ICP-MS with aerosol dilution is a reliable method for the direct analysis of liquid drug samples in order to attend the USP Chapters 232 and 233 requirements.

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Supplementary files

Article information


Submitted
01 Mar 2020
Accepted
21 May 2020
First published
21 May 2020

J. Anal. At. Spectrom., 2020, Accepted Manuscript
Article type
Paper

Direct analysis of liquid drugs by inductively coupled plasma mass spectrometry using aerosol dilution

P. Oliveira, G. G. A. Arantes de Carvalho and R. Lorencatto, J. Anal. At. Spectrom., 2020, Accepted Manuscript , DOI: 10.1039/D0JA00083C

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