Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Analysis

Editor-in-Chief

ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Establishment and Validation of an ICP-MS Method for Simultaneous Measurement of 24 Elemental Impurities in Ubenimex APIs According to USP/ICH guidelines

Author(s): Ming-Juan Zhao, Lei Cheng, Yu-Jia Huang, Ying Tao, Xiao Gu* and Jin-Qi Zheng*

Volume 17, Issue 6, 2021

Published on: 23 April, 2020

Page: [723 - 730] Pages: 8

DOI: 10.2174/1573412916999200423103711

Price: $65

Abstract

Background: To control the potential presence of heavy metals in pharmaceuticals, the United States Pharmacopeia (USP) and International Conference on Harmonization (ICH) have put forth new requirements and guidelines. USP <232> and ICH Q3D specify 24 elemental impurities and their concentration limits in consideration of the permitted daily exposure (PDE) of different drug categories (oral, parenteral and inhalation). while USP <233> describes more information about sample preparation and method validation procedure.

Objective: To establish and verify an ICP-MS method for the determination of 24 elemental impurities (Cd, Pb, As, Hg, Co, V, Ni, Tl, Au, Pd, Ir, Os, Ph, Ru, Se, Ag, Pt, Li, Sb, Ba, Mo, Cu, Sn, Cr) in ubenimex APIs according to USP/ICH guidelines.

Methods: Samples were analyzed by ICP-MS after direct dissolution in diluted acid solution. All elements were detected in He/HEHe mode (except for Li, which was in No gas mode).

Results: The spiked recoveries were within 80-120% except Hg (79.4% at 0.5J level in HEHe mode) and Cd (121.9% at 0.5J level in HE mode). The RSD of repeatability (N = 6) for all elements were < 7.0% and intermediate precision (N = 12) were < 9.0%. The correlation coefficients of linear (R) for 24 elements were all > 0.998. The Limits of Detection (LOD) were < 1 ng/mL except that Ni was 1.23 ng/mL in HEHe mode. The contents of 24 elements in 3 batches of samples were significantly lower than the actual target limit of ICH, while the highest content of Pd did not exceed 10 μg/g.

Conclusion: The established method was proved to be simple, sensitive and accurate. It successfully applied to the elemental impurity determination in 3 batches of ubenimex APIs from different manufactories. This method also provided technical guidance for the determination of multiple elements in pharmaceutical products.

Keywords: Elemental impurity, USP <233>, USP<232>, ICH Q3D, ICP-MS, ubenimex API.

« Previous Next »
Graphical Abstract

[1]
Liu, S.; Xie, F.; Wang, H.; Liu, Z.; Liu, X.; Sun, L.; Niu, Z. Ubenimex inhibits cell proliferation, migration and invasion in renal cell carcinoma: the effect is autophagy-associated. Oncol. Rep., 2015, 33(3), 1372-1380.
[http://dx.doi.org/10.3892/or.2014.3693] [PMID: 25571917]
[2]
Hitzerd, S.M.; Verbrugge, S.E.; Ossenkoppele, G.; Jansen, G.; Peters, G.J. Positioning of aminopeptidase inhibitors in next generation cancer therapy. Amino Acids, 2014, 46(4), 793-808.
[http://dx.doi.org/10.1007/s00726-013-1648-0] [PMID: 24385243]
[3]
Toshiyama, R.; Konno, M.; Eguchi, H.; Takemoto, H.; Noda, T.; Asai, A.; Koseki, J.; Haraguchi, N.; Ueda, Y.; Matsushita, K.; Asukai, K.; Ohashi, T.; Iwagami, Y.; Yamada, D.; Sakai, D.; Asaoka, T.; Kudo, T.; Kawamoto, K.; Gotoh, K.; Kobayashi, S.; Satoh, T.; Doki, Y.; Nishiyama, N.; Mori, M.; Ishii, H. Poly(ethylene glycol)-poly(lysine) block copolymer-ubenimex conjugate targets aminopeptidase N and exerts an antitumor effect in hepatocellular carcinoma stem cells. Oncogene, 2019, 38(2), 244-260.
[http://dx.doi.org/10.1038/s41388-018-0406-x] [PMID: 30089817]
[4]
Wickström, M.; Larsson, R.; Nygren, P.; Gullbo, J.; Aminopeptidase, N.; Aminopeptidase, N. CD13) as a target for cancer chemotherapy. Cancer Sci., 2011, 102(3), 501-508.
[http://dx.doi.org/10.1111/j.1349-7006.2010.01826.x ] [PMID: 21205077]
[5]
Han, L.; Zhao, Q.; Liang, X.; Wang, X.; Zhang, Z.; Ma, Z.; Zhao, M.; Wang, A.; Liu, S. Ubenimex enhances Brd4 inhibition by suppressing HEXIM1 autophagic degradation and suppressing the Akt pathway in glioma cells. Oncotarget, 2017, 8(28), 45643-45655.
[http://dx.doi.org/10.18632/oncotarget.17314 ] [PMID: 28484091]
[6]
Yamashita, M.; Wada, H.; Eguchi, H.; Ogawa, H.; Yamada, D.; Noda, T.; Asaoka, T.; Kawamoto, K.; Gotoh, K.; Umeshita, K.; Doki, Y.; Mori, M.A. CD13 inhibitor, ubenimex, synergistically enhances the effects of anticancer drugs in hepatocellular carcinoma. Int. J. Oncol., 2016, 49(1), 89-98.
[http://dx.doi.org/10.3892/ijo.2016.3496] [PMID: 27121124]
[7]
Jiang, Y.; Li, X.; Hou, J.; Huang, Y.; Wang, X.; Jia, Y.; Wang, Q.; Xu, W.; Zhang, J.; Zhang, Y. Synthesis and biological characterization of ubenimex-fluorouracil conjugates for anti-cancer therapy. Eur. J. Med. Chem., 2018, 143, 334-347.
[http://dx.doi.org/10.1016/j.ejmech.2017.11.074] [PMID: 29202398]
[8]
Jia, D.; Guo, L.; Jing, H. One case of fecal incontinence caused by ubenimex tablets. Chin. J. Clin. Rational Drug Use, 2018, 11(7A), 11-11.
[9]
Cui, H.; Meng, Z.; Ji, A.; Li, C.; Zhao, H.; Qu, Y. Synthesis of key intermediates of ubenimex. Zhongguo Yaowu Huaxue Zazhi, 2002, 12(3), 168-169.
[10]
Jia, M.; Wei, T.; Yang, K.; Xu, W. Overview of the synthesis of optically active 3-amino-2-hydroxy-4-phenylbutyric acids, key intermediates for numerous bioactive compounds. Mini Rev. Org. Chem., 2011, 8(2), 197-210.
[http://dx.doi.org/10.2174/157019311795177754]
[11]
Basavaraju, A.; Ramesh, A.B.; Jajcevic, D.; Heitmeir, F. Experimental parametric investigation of platinum catalysts using hydrogen fuel. Int. J. Hydrogen Energy, 2018, 43(46), 21307-21321.
[http://dx.doi.org/10.1016/j.ijhydene.2018.09.170]
[12]
Martins, A.R.; Carvalho, L.S.; Reyes, P.; Grau, J.M.; do Rangel, M.C. Hydrogen production on alumina-supported platinum catalysts. J. Mol. Catal. Chem., 2017, 429, 1-9.
[13]
Crampton, A.S. Hydrogenation reactions on small platinum clusters., Encyclopedia Interf. Chem., 2018, 465-476.
[http://dx.doi.org/10.1016/B978-0-12-409547-2.12984-1]
[14]
Lee, G.; Jeong, Y.J.; Kim, B.G.; Han, J.S.; Jeong, H.; Na, H.B.; Jung, J.C. Hydrogen production by catalytic decalin dehydro-genation over carbon-supported platinum catalyst: Effect of catalyst preparation method. Catal. Commun., 2015, 67, 40-44.
[http://dx.doi.org/10.1016/j.catcom.2015.04.002]
[15]
Fard, M.A.; Behnia, A.; Puddephatt, R.J. Stereochemistry of oxidative addition reactions of cycloneophyl complexes of Platinum(II): A methylene insertion reaction from dichloromethane. J. Organomet. Chem., 2019, 890, 32-42.
[http://dx.doi.org/10.1016/j.jorganchem.2019.03.022]
[16]
de Araujo, D.M.; Brito, C.D.; de Oliveira, S.D.S.; da Silva, D.R.; Martinez-Huitle, C.A.; Aragao, C.F.S. Platinum sensor for quantifying caffeine in drug formulations. Curr. Pharm. Anal., 2014, 10(4), 231-238.
[http://dx.doi.org/10.2174/1573412910666140630191329]
[17]
Rawat, K.S.; Garg, P.; Bhauriyal, P.; Pathak, B. Metal-ligand bifunctional based Mn-catalysts for CO2 hydrogenation reaction. Mol. Catal., 2019, 468, 109-116.
[http://dx.doi.org/10.1016/j.mcat.2019.02.017]
[18]
Inoué, S.; Yasuhara, A.; Ai, H.; Jr, M.F.H.; Murayama, M. Mn(II) oxidation catalyzed by nanohematite surfaces and manganite/hausmannite core-shell nanowire formation by self-catalytic reaction. Geochim. Cosmochim. Acta, 2019, 258, 79-96.
[http://dx.doi.org/10.1016/j.gca.2019.05.011]
[19]
Mutschler, R.; Moioli, E.; Züttel, A. Modelling the CO2 hydrogenation reaction over Co, Ni and Ru/Al2O3. J. Catal., 2019, 375, 193-201.
[http://dx.doi.org/10.1016/j.jcat.2019.05.023]
[20]
Kivrak, H. The effect of temperature and concentration for methanol electrooxidation on Pt-Ru catalyst synthesized by microwave assisted rote. Turk. J. Chem., 2015, 39, 563-575.
[http://dx.doi.org/10.3906/kim-1411-21]
[21]
Sahin1, O.; Kivrak, H.; Karaman1, M.; Atbas, D. The effect of iridium addition to platinum on the alcohol electrooxidation activity. Am. J. Materials Sci. Engg., 2015, 3(1), 15-20.
[22]
Çelik Kazıcı, H.; Caglar, A.; Aydogmus, T.; Aktas, N.; Kivrak, H. Microstructured prealloyed Titanium-Nickel powder as a novel nonenzymatic hydrogen peroxide sensor. J. Colloid Interface Sci., 2018, 530, 353-360.
[http://dx.doi.org/10.1016/j.jcis.2018.06.079 ] [PMID: 29982028]
[23]
Biró, L.P.; Márk, G.I.; Koós, A.A.; Horváth, Z.E.; Szabó, A.; Fonseca, A.; Nagy, J.B.; Colomer, J.F.; Lambin, Ph.; Meunier, V.; Charlier, J.C.; Bedoya-Martínez, O.N.; Hernández, E. Regularly curved carbon nanotubes. Fuller. Nanotub. Car. N., 2005, 13, 523-533.
[http://dx.doi.org/10.1081/FST-200039482]
[24]
Bagni, G.; Ravera, M.; Osella, D.; Mascini, M. Electrochemical biosensors as a screening tool of in vitro DNA-drug interaction. Curr. Pharm. Anal., 2005, 1(3), 217-224.
[http://dx.doi.org/10.2174/157341205774597904]
[25]
Gebel, T. Toxicology of platinum, palladium, rhodium, and their compounds.Anthropogenic Platinum-Group Element Emissions; Zereini, F; Alt, F., Ed.; Springer: Berlin, Heidelberg, 2000, pp. 245-255.
[http://dx.doi.org/10.1007/978-3-642-59678-0_25]
[26]
Vetter, M.H.; Khan, A.; Backes, F.J.; Bixel, K.; Cohn, D.E.; Copeland, L.J.; Fowler, J.M.; Salani, R.; Li, Q.; O’Malley, D.M. Outpatient desensitization of patients with moderate (high-risk) to severe platinum hypersensitivity reactions. Gynecol. Oncol., 2019, 152(2), 316-321.
[http://dx.doi.org/10.1016/j.ygyno.2018.10.037 ] [PMID: 30503265]
[27]
Pranczk, J.; Jacewicz, D.; Wyrzykowski, D.; Chmurzynski, L. Platinum(II) and palladium(II) complex compounds as anti-cancer drugs. Methods of cytotoxicity determination. Curr. Pharm. Anal., 2014, 10(1), 2-9.
[http://dx.doi.org/10.2174/157341291001140102103324]
[28]
Slawomir, C.; Jan, P.G.; Anna, P.T.; Anna, M.S-G. Nickel, Ruthenium, Rhodium, Palladium, Osmium, and Platinum.Patty’s Toxicology; Eula, B; Barbara, C., Ed.; Wiley & Sons, Inc.: New York, 2012, Vol. 1, pp. 653-768.
[29]
https://www.ema.europa.eu/en/documents/scientific-guideline/international-confere-nrence-harmonisation-technical-requirements-registration-pharmaceuticals-human-use_en-32.pdf2018. ]; Available from
[30]
Barin, J.S.; Mello, P.A.; Mesko, M.F.; Duarte, F.A.; Flores, E.M.M. Determination of elemental impurities in pharmaceutical products and related matrices by ICP-based methods: a review. Anal. Bioanal. Chem., 2016, 408(17), 4547-4566.
[http://dx.doi.org/10.1007/s00216-016-9471-6 ] [PMID: 27020927]
[31]
Qian, L.; Zhu, P.; Zhu, K.; Peng, J.; Zhou, F. Determination of trace palladium in zolpidem tartrate raw material by GFAAS. China Pharm., 2016, 27(6), 838-840.
[32]
Guo, W.; Li, L.; Li, S.; He, S.; Zheng, D. Establishment of monitoring method for residual palladium in tebipenem pivoxil. Food Drug, 2017, 19(3), 171-173.
[33]
Zhao, M.; Cheng, L.; Zhu, P.; Huang, L.; Gu, X.; Zheng, J. Determination of palladium residues in ubenimex by graphite furnace atomic absorption spectrometry., Strait Pharmaceut. J., 2020, 32(3)..
[34]
Chen, X.; Yang, X. Determination of B and Pd in obeticholic acid by ICP-AES. China Measurement Test, 2017, 43(2), 47-54.
[35]
Lai, Y.; Zou, Y.; Xu, S. Determination of palladium residues in anastrozole by ICP-AES after pretreatment with ashing. Physical Testing Chem.Anal.Part B: Chem. Anal., 2014, 50, 247-248.
[36]
Seubert, A.; Rasheed, A.S. Separation of metal-trifluoperazine hydrochloride complexes using zwitterionic ion chromatography (zic) coupled online with ICP-AES. Curr. Pharm. Anal., 2017, 13(4), 328-333.
[http://dx.doi.org/10.2174/1573412912666160720114147]
[37]
Chahrour, O.; Malone, J.; Collins, M.; Salmon, V.; Greenan, C.; Bombardier, A.; Ma, Z.; Dunwoody, N. Development and validation of an ICP-MS method for the determination of elemental impurities in TP-6076 active pharmaceutical ingredient (API) according to USP (232)/(233). J. Pharm. Biomed. Anal., 2017, 145, 84-90.
[http://dx.doi.org/10.1016/j.jpba.2017.06.045 ] [PMID: 28654780]
[38]
Carr, J.E.; Dill, A.E.; Kwok, K.; Carnahan, J.W.; Webster, G.K. LC-ICP-MS for nonmetal selective detection of pharmaceuticals. Curr. Pharm. Anal., 2008, 4(4), 206-214.
[http://dx.doi.org/10.2174/157341208786306234]
[39]
Bendakovská, L.; Krejčová, A.; Černohorský, T.; Zelenkovetá, J. Development of ICP-MS and ICP-OES methods for determination of gadolinium in samples related to hospital waste water treatment. Chem. Pap., 2016, 70(9), 1155-1165.
[http://dx.doi.org/10.1515/chempap-2016-0057]
[40]
Vanhaecke, F.; Van Hoecke, K.; Catry, C. Optimization of sample preparation and a quadrupole ICP-MS measurement protocol for the determination of elemental impurities in pharmaceutical substances in compliance with USP guidelines. J. Anal. At. Spectrom., 2012, 27, 1909-1919.
[http://dx.doi.org/10.1039/c2ja30128h]
[41]
Liu, S. Study on electrochemical properties of palladium in high acid media., Master Thesis, Shanghai Jiao Tong University: Shanghai, 2013. February.

Rights & Permissions Print Cite
Article Metrics
28
1
© 2024 Bentham Science Publishers | Privacy Policy