DOI: https://doi.org/10.15421/081711

PHARMACOPOEIA METHODS FOR ELEMENTAL ANALYSIS OF MEDICINES: A COMPARATIVE STUDY

Tetiana M. Derkach, Olga P. Baula

Abstract


The article is devoted to the problem of quality assurance of medicinal products, namely the determination of elemental impurity concentration compared to permitted daily exposures for and the correct choice analytical methods that are adequate to the formulated tasks. The paper goal is to compare characteristics of four analytical methods recommended by the Pharmacopoeia of various countries to control the content of elemental impurities in medicines, including medicinal plant raw materials and herbal medicines. Both advantages and disadvantages were described for atomic absorption spectroscopy with various atomising techniques, as well as atomic emission spectroscopy and mass spectrometry with inductively coupled plasma. The choice of the most rational analysis method depends on a research task and is reasoned from the viewpoint of analytical objectives, possible complications, performance attributes, and economic considerations. The methods of ICP-MS and GFAAS were shown to provide the greatest potential for determining the low and ultra-low concentrations of chemical elements in medicinal plants and herbal medicinal products. The other two methods, FAAS and ICP-AES, are limited to the analysis of the main essential elements and the largest impurities. The ICP-MS is the most efficient method for determining ultra-low concentrations. However, the interference of mass peaks is typical for ICP-MS. It is formed not only by impurities but also by polyatomic ions with the participation of argon, as well as atoms of gases from the air (C, N and O) or matrices (O, N, H, P, S and Cl). Therefore, a correct sample preparation, which guarantees minimisation of impurity contamination and loss of analytes becomes the most crucial stage of analytical applications of ICP-MS. The detections limits for some chemical elements, which content is regulated in modern Pharmacopoeia, were estimated for each method and analysis conditions of medicinal plant raw materials and herbal medicinal products.


Keywords


elemental impurities; atomic absorption and emission spectroscopy; mass-spectrometry; inductively-coupled plasma; detection limit; pharmacopoeia; medicinal herbs; herbal medicinal product

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References


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References

US Pharmacopeia. (2013). <232> Elemental Impurities – Limits. (39 ed., pp.151-153). The US Pharmacopeial Convention.

Q3D Elemental Impurities. Guidance for Industry. (2015). USA: ICH.

Guideline on the specification limits for residues of metal catalysts or metal reagents. (2008). (European Medicines Agency, Doc. Ref. EMEA/CHMP/SWP/4446/2000). –London: EMA.

Yan, X. L., Lin, L. Y., Liao, X. Y., Zhang, W. B. (2012). Arsenic accumulation and resistance mechanism in Panax notoginseng, a traditional rare medicinal herb. Chemosphere, 87, 31–36. doi: 10.1016/j.chemosphere.2011.11.049

Barthwal, J., Nair, S., Kakkar, P. (2008). Heavy Metal Accumulation in Medicinal Plants Collected from Environmentally Different Sites. Biomed. Environ. Sci., 21, 319-324. doi: 10.1016/S0895-3988(08)60049-5

Okem, A., Southway, C., Ndhlala, A. R., Van Staden, J. (2012). Determination of total and bioavailable heavy and trace metals in South African commercial herbal concoctions using ICP-OES. S. Afr J. Botany, 82, 75–82. doi: 10.1016/j.sajb.2012.07.005

Gupta, S., Pandotra, P., Gupta, A.P., Dhar, J.K., Sharma, G., Ram, G., Husain, M.K., Bedi, Y.S. (2010). Volatile (As and Hg) and non-volatile (Pb and Cd) toxic heavy metals analysis in rhizome of Zingiber officinale collected from different locations of North Western Himalayas by Atomic Absorption Spectroscopy. Food Chem. Toxicol., 48, 2966–2971. doi:10.1016/j.fct.2010.07.034

Muller, A. L. H., Oliveira, J. S. S., Mello, P. A., Muller, E. I., Flores, E. M. M. (2015). Study and determination of elemental impurities by ICP-MS in active pharmaceutical ingredients using single reaction chamber digestion in compliance with USP requirements. Talanta, 136, 161–169. http://dx.doi.org/10.1016/j.talanta.2014.12.023

Li, G., Schoneker, D., Ulman, K. L., Sturm, J. J., Thackery, L. M., Kauffman, J. F. (2015). Elemental Impurities in Pharmaceutical Excipients. J. Pharmac. Sci., 104, 4197–4206. DOI 10.1002/jps.24650

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

Støvinga, C., Jensen, H., Gammelgaard, B., Stürup, B. (2013). Development and validation of an ICP-OES method for quantitation of elemental impurities in tablets according to coming US pharmacopeia chapters. J. Pharmac. Biomed. Anal., 84, 209– 214. http://dx.doi.org/10.1016/j.jpba.2013.06.007

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Balcaen, L., Bolea-Fernandez, E., Resano, M., Vanhaecke, F. (2015). Inductively coupled plasma - Tandem mass spectrometry (ICP-MS/MS): A powerful and universal tool for the interference-free determination of (ultra)trace elements - A tutorial review. Anal. Chim. Acta, 894, 7-19. http://dx.doi.org/10.1016/j.aca.2015.08.053

Singh, S., Handa, T., Narayanam, M., Sahu, A., Junwal, M., Shah, R. P. (2012). A critical review on the use of modern sophisticated hyphenated tools in the characterization of impurities and degradation products. J. Pharmac. Biomed. Anal., 69, 148– 173. http://dx.doi.org/10.1016/j.jpba.2012.03.044

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

Hill, S. J., Fisher, A., Foulkes, M. (2008). Basic Concepts and Instrumentation for Plasma Spectrometry. In S. J. Hill (Ed.), Inductively Coupled Plasma Spectrometry and its Applications (2nd ed., pp. 88-90). New York, USA: John Wiley & Sons.

Kaushik, D., Pandey, M. K., Sharma, A. (2014). Current issues in Authentication and Quality control of Natural Products. Res. Plant. Biol., 4(5), 57-64.

Tyler, G. (1992). AA or ICP - which do you choose? Chemistry in Australia. 59(4), 150-152.

Tyler, G. ICP-OES, ICP-MS and AAS Techniques Compared. In: ICP Optical Emission Spectroscopy. Technical Note 05. J. Yvon S.A.S, Horiba Group, Longjumeau, France. Retrieved from http://www.horiba.com/fileadmin/uploads/Scientific/Downloads/OpticalSchool_CN/TN/ICP/ICP-OES__ICP-MS_and_AAS_Techniques_Compared.pdf

Tyler, G. (1994). ICP-MS, or ICP-AES and AAS?—a comparison. Australia: Varian.

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Fassel, V. A., Kniseley, R. N. (1974). Inductively coupled plasmas. Anal. Chem., 46(13), 1155–1164.

Fuller, C.W. (1977). Electrothermal Atomization for Atomic Absorption Spectrometry. London, UK: The Chemical Society.

AAS, GFAAS, ICP or ICP-MS? Which technique should I use? An elementary overview of elemental analysis. (2001). U.S.A: Thermo Elemental. Retrieved from http://www.thermo.com/eThermo/CMA/PDFs/Articles/articlesFile_18407.pdf


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