Objective: To establish an HPLC-ELSD method for detection of related substances in penicillamine tablets, and analyze the quality of related substances in domestic penicillamine tablets. Methods: HPLC-ELSD method was established for the detection of related substances in 31 batches of penicillamine tablets and 6 batches of penicillamine raw materials. The chemical structures of six impurities were predicted by HPLC-MSn with double ternary column switching, and their sources were analyzed. Results: The number and content of related substances in penicillamine tablets were much higher than those in raw materials. Among the six impurities, penicillamine disulfide was known impurity, five were unknown impurities, and all of them were degradation impurities. ADMET Predictor results showed that the toxicity of 4 impurities were greater than penicillamine, 2 impurities were equivalent to that of penicillamine. Conclusion: The HPLC-ELSD method is suitable for the detection of related substances in penicillamine tablets. The impurities in the preparation mainly come from the production process of the preparation. The risk of related substances in penicillamine tablets is relatively high. Based on the results of toxicity prediction of impurities, it is suggested that pharmaceutical manufacturers should attach great importance to all aspects of pharmaceutical production.
WANG Li-ping
. Analysis of related substances in penicillamine tablets[J]. Chinese Journal of Pharmaceutical Analysis, 2022
, 42(4)
: 684
-692
.
DOI: 10.16155/j.0254-1793.2022.04.16
[1] DAVIS P. Penicillamine metal chelates and their possible importance in rheumatoid arthritis-a brief review[J].Clin Invest Med, 1984, 7(1):41
[2] CLAPELA R, ZUNIGA G, SEIMAN M. D-penicillamine in the therapy of fibrotic lung diseases[J].Int J Clin Pharmacol Ther Toxicol, 1986, 24(1):16
[3] 中华人民共和国药典2020年版. 二部[S].2020:738
ChP 2020.Vol Ⅱ[S].2020:738
[4] USP 42-NF 37. VolⅡ[S].2019:3403
[5] EP 10.0. Vol Ⅱ[S].2021:3498
[6] BP. Vol Ⅱ[S].2021:554
[7] 李茜, 宋汉敏,刘英.离子色谱法测定青霉胺片的含量及有关物质[J].药物分析杂志, 2020, 40(4):698
LI Q, SONG HM, LIU Y. Determination of penicillamine tablets and its related substances by ion chromatography[J].Chin J Pharm Anal,2020, 40(4):698
[8] 王建, 胡小君, 倪坤仪. HPLC-ELSD和HPLC-MSn分析硫酸奈替米星及其注射液[J].中国药学杂志, 2006, 41(16):1268
WANG J, HU XJ, NI KY. Determination of netimicin sulfate and its related substances by HPLC-ELSD and HPLC-MSn[J].Chin Pharm J, 2006, 41(16):1268
[9] 袁耀佐, 张玫, 钱文, 等. 高效液相色谱-电喷雾-离子阱质谱法快速推定硫酸奈替米星中有关物质的结构[J].中国药学杂志, 2010, 45(18):1428
YUAN YZ, ZHANG M, QIAN W, et al. Rapid characterization of the related substances in netimicin sulfate sample by HPLC-ESI-IT-MSn[J].Chin Pharm J, 2010, 45(18):1428
[10] 田冶, 韩莹, 胡昌勤. 注射用盐酸头孢替安杂质谱研究[J].中国新药杂志, 2019, 28(5):513
TIAN Y, HAN Y, HU CQ. Impurity profile study of cefotiam hydrochloride for injection[J].Chin J New Drugs, 2019, 28(5):513
[11] 李倚天, 李茜,王立萍,等.青霉胺片的质量评价[J].中国抗生素杂志,2021, 46(3):244
LI YT, LI Q, WANG LP, et al. Quality evaluation of penicillaminetablets[J].Chin J Antibiot,2021, 46(3):244
