Oxidized related substance of methionine in compound amino acid injection (18AA-Ⅱ)

SHAO Tianshu; ZHOU Changming; LI Hui; GUO Lei

doi:10.11665/j.issn.1000-5048.20210609

Journal of China Pharmaceutical University > 2021 > 52(6): 713-718. > DOI: 10.11665/j.issn.1000-5048.20210609

SHAO Tianshu, ZHOU Changming, LI Hui, GUO Lei. Oxidized related substance of methionine in compound amino acid injection (18AA-Ⅱ)[J]. Journal of China Pharmaceutical University, 2021, 52(6): 713-718. DOI: 10.11665/j.issn.1000-5048.20210609

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Oxidized related substance of methionine in compound amino acid injection (18AA-Ⅱ)

NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Beijing Institute of Drug Control, Beijing 102206, China

Funds: This study was supported by the National Drug Evaluation Surveillance (2019)

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Received Date: May 20, 2021
Revised Date: November 05, 2021

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Abstract

TA method for the content determination of methionine sulfoxide and methionine sulfone in compound amino acid injection (18AA-II) was established in order to investigate their level in 155 batches of this product, and to explore the reason for the generation of these two impurities.The determination was performed on an Agilent Poroshell 120 EC-C₁₈ column with mobile phases of sodium acetate/tetrahydrofuran solution (A) and sodium acetate solution -acetonitrile-methanol (B, 200∶400∶400) (gradient elution) at the flow rate of 0.5 mL/min.The excitation wavelength and the emission wavelength of the fluorescence detector were 233 nm and 441 nm, respectively.The column temperature was 40 °C, and the injection volume was 8 μL.The contents of methionine sulfoxide and methionine sulfone from 155 batches of compound amino acid injection (18AA-II) was determined using this method, and the residual oxygen content was detected by headspace gas analyzer.The results showed that the linear range of methionine sulfoxide and methionine sulfone were 0.128 1-10.250 0 μg/mL (r = 0.999 9) and 0.261 0-10.440 0 μg/mL (r = 0.999 8), respectively.The limits of quantitation were 0.13 μg/mL and 0.26 μg/mL, respectively; the limits of detection were 0.04 μg/mL and 0.09 μg/mL, respectively.RSDs of precision, stability and repetitive test were all lower than 1.3%.The recoveries ranged 98.00%-100.79% (RSD = 1.15%, n = 9) and 98.19%-102.31% (RSD = 1.33%, n = 9).The content level of oxidized related substances from different manufacturers showed significant difference, showing relevance with the residual oxygen content to some extent, yet no significant correlation with the added amount of antioxygen (sodium pyrosulfite).The method is validated to be useful for the content control of methionine sulfoxide and methionine sulfone in compound amino acid injection (18AA-II).It is quite necessary to include the determination of oxidized related substance into the quality specification.Manufacturers should strengthen the control of remaining oxygen in their products.
- compound amino acid injection,
- methionine,
- oxidized related substance,
- determination of content

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[1]	. Chin J New Drugs（中国新药杂志），2019，28（5）：584-588.
[2]	Zhou M，Xiong X，Wang X，et al. Quality evaluation of amino acid injection（18AA）［J］. Drug Res（药物研究），2020，17（23）：20-22.
[3]	Gao C，Li M，Wei JM，et al. Expert consensus on clinical use of compound amino acid injection［J］. Electron J Metab Nutr Cancer （肿瘤代谢与营养电子杂志），2019，6（2）：183-189.
[4]	Joseph TD，Adnan AE. L-methionine-dl-sulfoxide metabolism and toxicity in freshly isolated mouse hepatocytes：gender differences and inhibition with aminooxyacetic acid［J］. Drug Metab Dispos，2008，36（11）： 2252-2260.
[5]	Joseph TD，Adnan AE. The biochemical and toxicological significance of hypermethionemia： new insights and clinical relevance［J］. Expert Opin Drug Met，2010，6 （11）：1333-1346.
[6]	Arad G，Kulka RG. Effects of glutamine，methionine sulfone and dexamethasone on rates of synthesis of glutamine synthetase in cultured hepatoma cells［J］.Biochimica et BiophysicaActa，1978，544（1）：153-162.
[7]	Chinese Pharmacopoeia Commission. Chinese Pharmacopoeia：part 2（中华人民共和国药典：二部）［S］. Beijing：China Medical Science Press，2020：811.
[8]	Xiao YX，Ni JH. The determination of met，metson and metsox in gelatins［J］. J Amino Acid（氨基酸杂志），1994，1：31-34.
[9]	Li L，Cui HY，Zhong JQ，et al. Simultaneous and direct determination of methionine sulfoxide and methionine sulfone in compound amino acid injection （18AA） by HPLC［J］. Chin J Anal Lab（分析试验室），2018，37（11）：1309-1314.
[10]	Kan WN，Teng YK，Yang HW，et al. Simultaneous determination of 18 kinds of amino acids in compound amino acid injection by DTDPA-PITC combined with pre-column derivatization HPLC［J］. J China Pharm（中国药房），2014，25（12）：1122-1125.
[11]	Wang Z，Feng F. Determination of 12 depression-related amino acids in rat plasma and brain tissue by HPLC with pre-column derivatization［J］. J China Pharm Univ（中国药科大学学报），2012，43（4）：345-349.
[12]	Chinese Pharmacopoeia Commission. Chinese Pharmacopoeia：part 4（中华人民共和国药典：四部）［S］. Beijing：China Medical Science Press，2020.
[13]	ICH.Q3B（R2）：impurities in new drug products［EB/OL］.2006.［2021-04-27］. https：//database.ich.org/sites/default/files/Q3B%28R2%29%20Guideline.pdf

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