TY - JOUR

T1 - Development and validation of an ICP-OES method for quantitation of elemental impurities in tablets according to coming US pharmacopeia chapters

AU - Jensen, Celina Støving

AU - Jensen, Henrik

AU - Gammelgaard, Bente

AU - Stürup, Stefan

N1 - Copyright © 2013 Elsevier B.V. All rights reserved.

PY - 2013/10

Y1 - 2013/10

N2 - May 1, 2014 the United States Pharmacopeia (USP) will implement two new chapters stating limit concentrations of elemental impurities in pharmaceuticals applying inductively coupled plasma methods. In the present work an inductively coupled plasma optical emission spectrometry (ICP-OES) method for quantitation of As, Cd, Cu, Cr, Fe, Hg, Ir, Mn, Mo, Ni, Os, Pb, Pd, Pt, Rh, Ru, V and Zn in tablets according to the new USP chapters was developed. Sample preparation was performed by microwave-assisted acid digestion using a mixture of 65% HNO3 and 37% HCl (3:1, v/v). Limits of detection and quantitation were at least a factor of ten below the USP limit concentrations showing that the ICP-OES technique is well suited for quantitation of elemental impurities. Excluding Os, spike recoveries in the range of 85.3-103.8% were obtained with relative standard deviations (%RSD) ranging from 1.3 to 3.2%. Due to memory effects the spike recovery and %RSD of Os were 161.5% and 13.7%, respectively, thus the method will need further development with respect to elimination of the memory effect of Os. The method was proven to be specific but with potential spectral interference for Ir, Os, Pb, Pt and Rh necessitating visual examination of the spectra. Hg memory effect was handled by using lower spike levels combined with rinsing with 0.1M HCl. The tablets had a content of Fe and Pt of 182.8±18.1 and 2.8±0.2μg/g, respectively and did therefore not exceed the limit concentration defined by USP. It is suggested that the developed method is applicable to pharmaceutical products with a composition and maximal amount of daily intake (g drug product/day) similar to the tablets used in this work.

AB - May 1, 2014 the United States Pharmacopeia (USP) will implement two new chapters stating limit concentrations of elemental impurities in pharmaceuticals applying inductively coupled plasma methods. In the present work an inductively coupled plasma optical emission spectrometry (ICP-OES) method for quantitation of As, Cd, Cu, Cr, Fe, Hg, Ir, Mn, Mo, Ni, Os, Pb, Pd, Pt, Rh, Ru, V and Zn in tablets according to the new USP chapters was developed. Sample preparation was performed by microwave-assisted acid digestion using a mixture of 65% HNO3 and 37% HCl (3:1, v/v). Limits of detection and quantitation were at least a factor of ten below the USP limit concentrations showing that the ICP-OES technique is well suited for quantitation of elemental impurities. Excluding Os, spike recoveries in the range of 85.3-103.8% were obtained with relative standard deviations (%RSD) ranging from 1.3 to 3.2%. Due to memory effects the spike recovery and %RSD of Os were 161.5% and 13.7%, respectively, thus the method will need further development with respect to elimination of the memory effect of Os. The method was proven to be specific but with potential spectral interference for Ir, Os, Pb, Pt and Rh necessitating visual examination of the spectra. Hg memory effect was handled by using lower spike levels combined with rinsing with 0.1M HCl. The tablets had a content of Fe and Pt of 182.8±18.1 and 2.8±0.2μg/g, respectively and did therefore not exceed the limit concentration defined by USP. It is suggested that the developed method is applicable to pharmaceutical products with a composition and maximal amount of daily intake (g drug product/day) similar to the tablets used in this work.

U2 - 10.1016/j.jpba.2013.06.007

DO - 10.1016/j.jpba.2013.06.007

M3 - Journal article

C2 - 23850936

VL - 84

SP - 209

EP - 214

JO - Journal of Pharmaceutical and Biomedical Analysis

JF - Journal of Pharmaceutical and Biomedical Analysis

SN - 0731-7085

ER -