Determination of Elemental Impurities in Acyclovir Ointment and Raw Materials Using Microwave Acid Digestion (MW-AD) and ICP-MS

Mario H Gonzalez,Jéssica S Coelho,Caroline S Da Silva,Ana Rita A Nogueira,Silmara R Bianchi,Clarice D B Amaral,Luciano H B De Oliveira,Andrea Oliveira

doi:10.5935/0103-5053.20160151

Mario H Gonzalez, Jéssica S Coelho + Show 6 more

Open Access

https://doi.org/10.5935/0103-5053.20160151

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Abstract

Inorganic elements present in pharmaceutical products were determined by inductively coupled plasma-mass spectrometer (ICP-MS), employing microwave acid digestion as a sample preparation method. The most abundant isotopes, 75As+ , 65Cu+ , 52Cr+ , 58Ni+ , 208Pb+ , and 51V+ , were determined in acyclovir ointment and its constituents. Elemental impurities in the pharmaceutical samples were determined using an inductively coupled plasma-universal cell technology-mass spectrometer (ICP-UCT-MS) operated in kinetic energy discrimination (KED) and standard mode. The accuracy of the method was assessed by means of addition and recovery experiments. Except for Cr, spiked recoveries of the elements added to the samples before microwave acid digestion (MW-AD) step were between 95.1 and 126%, and after MW-AD step ranged from 85.6 to 132%. Limits of detection (LOD) obtained by proposed method is in agreement to those required by the U.S. Pharmacopeia Convention (USP), showing that the ICP-MS technique is well suited for quantification of these elements. The LOD?s (ng L-1) for 51V+ , 52Cr+ , 58Ni+ , 65Cu+ , 75As+ and 208Pb+ in 1% v v-1 HNO3 medium were: 2.2, 81.3, 91.9, 6.9, 0.2 and 3.1, respectively. The concentration of the analytes in these samples presented a wide range, varying from 2.3 ± 0.8 µg kg-1 for As to 3446 ± 47 µg kg-1 for Cr.

Highlights

Brazil currently ranks sixth in the world pharmaceutical market, and economic growth in this sector indicates that by 2016, Brazil will be ranked fourth.[1]
The aim of this study was to optimize a microwave acid digestion (MW-AD) procedure for simultaneous determination of As, Cu, Cr, Ni, Pb and V by inductively coupled plasma-mass spectrometer (ICP-MS) employing the standard mode, which allows the ICP‐MS to be operated with the cell turned off, and second ICP‐MS determination method evaluated was the kinetic energy discrimination (KED) mode, in acyclovir ointment and their manufacturer products disodium edetate, acyclovir active pharmaceutical ingredients (API), non-ionic emulsifying wax, and methylparaben
Reference analytical solution for ICP-MS analysis were prepared before use by serial dilutions of stock solutions containing 1000 mg L-1 of As, Cr, Cu, Ni, Pb and V (Fluka, Buchs, Switzerland) in solution containing 1% v v-1 of HNO3

Summary

Introduction

Brazil currently ranks sixth in the world pharmaceutical market, and economic growth in this sector indicates that by 2016, Brazil will be ranked fourth.[1] Globally, pharmaceuticals constitute a promising market, as evidenced by a survey conducted by Scrip Insights, which showed that total pharmaceutical retail sales in 2011 were approximate US$ 25.8 billion. Accompanying this expansion of the pharmaceutical market is a search for better quality medicines.[2,3]. The primary references are the United States Pharmacopeia (USP) and the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Food and Drug Administration (FDA).[4]

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