ICP-OES elemental impurities study on different pharmaceutical dosage forms of Ibuprofen using microwave-assisted digestion procedure

Katerina Jancevska, Gjorgji Petrushevski, Mirjana Bogdanoska, Trajce Stafilov, Sonja Ugarkovic


Fast and simple closed-vessel microwave-assisted digestion procedure was developed for decomposition of three pharmaceutical dosage forms of ibuprofen such as tablets, suspension and gel, prior to elemental impurity analysis by one robust and precise ICP-OES method. Samples were digested by four-step microwave program consisting of a 10 min temperature gradient to 180°C, maintained at 180°C for 10 min, followed by 5 min ramping time to 210°C with holding time of 10 min on 210°C. Subsequently, ICP-OES method was developed and validated for simultaneous determination of selected elemental impurities. Results of recovery studies range between 77% and 105% for each element in all analyzed formulations. Correlation coefficients of the regression equations were higher than 0.999 for all analyzed elements. Validation results reveal that the proposed method is specific, accurate, and precise and could be applied for simultaneous quantitative analysis of multi element solutions in different pharmaceutical dosage forms of ibuprofen.


Pharmaceutical; Elemental impurities; Microwave-assisted digestion; Inductively coupled plasma; Ibuprofen

Full Text:



International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. ICH harmonized guideline: guideline for elemental impurities – Q3D (R1). European Medicines Agency; 2019.

The United States Pharmacopeial Convention. The United States Pharmacopoeia, USP 40-NF 35, Chapter 232: Elemental Impurities- Limits, Revis Bull, Official. 8065–8069, 2017.

The United States Pharmacopeial Convention. The United States Pharmacopoeia, USP 38-NF 33, Chapter 233: Elemental Impurities- Procedures, Revis Bull, Official. 232–234, 2015.

European Pharmacopeia 9.0 edition (supplement 9.6). Vol 1. Strasbourg Cedex: Council of Europe, Chapter 2.4.20. Determination of Elemental Impurities, 5833–5836, 2018.

S. Bennis, L. Yachi, H. Ouhaddouch H, M. Alami Chentoufi, A Cheikh, M Bouatia, 5PSQ-112 risk assessment of elemental impurities for manufacturing the drug substance (ICH Q3D), Eur J Hosp Pharm. 26 (1), A1–A311 (2019).

R. D. Koons, ICP emission spectrometry: a practical guide by Joachim N€olte; Wiley. J Am Chem Soc. 125, 16154, 2003.

M. Maithani, R. Raturi, P. Sharma, V. Gupta, P. Bansal, Elemental impurities in pharmaceutical products adding fuel to the fire. Regul Toxicol Pharmacol. 108, 104435 (2019), DOI: 10.1016/j.yrtph.2019.104435.

P. Pohl, A. Bielawska-Pohl, A. Dzimitrowicz, Impact and practicability of recently introduced requirements on elemental impurities. TrAC Trends Anal Chem. 101, 43–55 (2018), DOI: 10.1016/j.trac.2017.09.011.

V. Balaram, Recent advances in the determination of elemental impurities in pharmaceuticals – status, challenges and moving frontiers. TrAC Trends Anal Chem. 80, 83–95 (2016), DOI: 10.1016/j.trac.2016.02.001.

K. Janchevska, T. Stafilov, S. Memed-Sejfulah, M. Bogdanoska, S. Ugarkovic, G. Petrushevski, ICH Q3D based elemental impurities study in liquid pharmaceutical dosage form with high daily intake – comparative analysis by ICP-OES and ICP-MS, Drug Dev Ind Pharm. 46 (3), 456-461 (2020), DOI: 10.1080/03639045.2020.1724136.

C. Støving, H. Jensen, B. Gammelgaard, S. Stefan, Development and validation of an ICP-OES method for quantitation of elemental impurities in tablets according to coming US Pharmacopeia chapters. J Pharm Biomed Anal. 84, 209–214 (2013), DOI: 10.1016/j.jpba.2013.06.007.

Q. Tu, T. Wang, V. Antonucci, High-efficiency sample preparation with dimethylformamide for multi-element determination in pharmaceutical materials by ICP-AES. J Pharm Biomed Anal. 52 (2), 311–315 (2010), DOI: 10.1016/j.jpba.2010.01.008.

N. Lewen, The use of atomic spectroscopy in the pharmaceutical industry for the determination of trace elements in pharmaceuticals. J Pharm Biomed Anal. 55 (4), 653-661 (2011), DOI: 10.1016/j.jpba.2010.11.030.

J.S. Barin, P.A Mello, M.F. Mesko, F. A. Duarte, E. M. Flores, Determination of elemental impurities in pharmaceutical products and related matrices by ICP-based methods: a review. Anal Bioanal Chem. 408 (17), 4547–4566 (2016), DOI: 10.1007/s00216-016-9471-6.

J- L. Todoli, J-M. Mermet. Acid interferences in atomic spectrometry: analyte signal effects and subsequent reduction. Spectrochim Acta B. 54 (6), 895–929 (1999).

M. Wasilewska, W. Goessler, M. Zischka, B. Maichin, G. Knapp. Efficiency of oxidation in wet digestion procedures and influence from the residual organic carbon content on selected techniques for determination of trace elements. J. Anal. At. Spectrom. 17 (9), 1121–1125 (2002), DOI: 10.1039/B200644H.

F.C. Pinheiro, A.I. Barros, A.J. Nóbrega, Evaluation of dilute-and-shoot procedure for determination of inorganic impurities in liquid pharmaceutical samples by ICP OES. Microchem.J. 146, 948-956 (2019), DOI: 10.1016/j.microc.2019.02.021.

J.S. Barin, B. Tischer, R.S. Picoloto, F.G. Antes, F.E. B. da Silva, F.R. Paula, E.M.M. Flores, Determination of toxic elements in tricyclic active pharmaceutical ingredients by ICP-MS: a critical study of digestion methods. J. Anal. At. Spectrom. 29 (2), 352-358 (2014), DOI: 10.1039/C3JA50334H.

F.C. Pinheiro, D.V. Babos, A.I. Barros, E.R. Pereira-Filho, A.J. Nóbrega, Microwave-assisted digestion using dilute nitric acid solution and investigation of calibration strategies for determination of As, Cd, Hg and Pb in dietary supplements using ICP-MS. J. Pharm. Biomed. Anal. 174, 471-478 (2019), DOI: 10.1016/j.jpba.2019.06.018.

F.C. Pinheiro, A.I. Barros, A.J. Nóbrega. Microwave-assisted sample preparation of medicines for determination of elemental impurities in compliance with United States Pharmacopeia: How simple can it be? Anal.Chim. 1065, 1-11 (2019), DOI: 10.1016/j.aca.2019.03.016.

D. W. Kaufman, J.P. Kelly, D.R. Battista, M.K. Malone, R.B. Weinstein, S. Shiffman, Exceeding the daily dosing limit of nonsteroidal anti‐inflammatory drugs among ibuprofen users. Pharmacoepidemiol Drug Saf. 27 (3), 322-331, (2018), DOI: 10.1002/pds.4391.

F. De Logu, S. Li Puma, L. Landini, T. Tuccinardi, G. Poli, D. Preti, G. De Siena, R. Patacchini, M. G. Tsagareli, P. Gepperii, R. Nassini, The acyl-glucuronide metabolite of ibuprofen has analgesic and anti-inflammatory effects via the TRPA1 channel. Pharmacological Research. 142, 127-139 (2019), DOI: 10.1016/j.phrs.2019.02.019.

Riley CM, Rosanske TW, Riley S. Specification of drug substances and products: development and validation of analytical methods. Amsterdam; Waltham (MA): Elsevier; 2014

A. Shrivastava, V. Gupta, Methods for the Determination of Limit of Detection and Limit of Quantitation of the Analytical Methods. Chronicles Young Sci. 2 (1), 21 (2011), DOI: 10.4103/2229-5186.79345.

P. W. J. M. Boumans, Detection Limits and Spectral Interferences in Atomic Emission Spectrometry. Anal. Chem. 66 (8), 459A-467A (1994), DOI: 10.1021/ac00080a001.

L. V. Rajaković, D. D. Marković, V. N. Rajaković-Ognjanović, D. Z. Antanasijević, Review: The Approaches for Estimation of Limit of Detection for ICP-MS Trace Analysis of Arsenic. Talanta. 102, 79–87 (2012), DOI: 10.1016/j.talanta.2012.08.016.

D. Ziental, B. Czarczynska-Goslinska, T. M. Dariusz, A. Glowacka-Sobotta, B. Stanisz, T. Goslinski, L. Sobotta, Review: Titanium Dioxide Nanoparticles: Prospects and Applications in Medicine. Nanomaterials. 10 (2), 387 (2020), DOI: 10.3390/nano10020387.

DOI: http://dx.doi.org/10.20450/mjcce.2021.2100


  • There are currently no refbacks.

Copyright (c) 2021 Katerina Jancevska, Gjorgji Petrushevski, Mirjana Bogdanoska, Trajce Stafilov, Sonja Ugarkovic

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.