Identification,characterization, and synthesis of process-related impurities in antiproliferative agent TQ-B3203 |
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| Authors: | Xiquan Zhang Meng Cao Jing Xing Ming Zheng Fei Liu Ping Dong |
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| Institution: | 1. School of Biological Science &2. Medical Engineering, Southeast University, Nanjing, China;3. Nanjing Institute of Pharmaceutical Research and Development, Chia-tai Tianqing Pharmaceutical Group Co. Ltd, Nanjing, China;4. Suzhou Southeast Pharmaceuticals Co. Ltd, Suzhou, China;5. Nanjing Institute of Pharmaceutical Research and Development, Chia-tai Tianqing Pharmaceutical Group Co. Ltd, Nanjing, China |
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| Abstract: | Liposoluble camptothecin derivative, research name TQ-B3203, is a recently developed investigational antiproliferative agent by our group. The structure of TQ-B3203 is 2-(hexadecyloxycarbonyl)-2,5,7,8-tetramethylchroman-6-yl 7-ethyl-camptothecin-10-yl succinate, containing an SN-38 component, a trolox component, a succinic acid linker, and a hexadecanol chain. In this study, the process-related impurities of bulk TQ-B3203 were identified, characterized, and synthesized. Seven major impurities were revealed based on the mass spectrum (MS) and nuclear magnetic resonance (NMR) spectral data. They were characterized as SN-38 (IMP-I), trolox (IMP-II), 2-(dodecyloxycarbonyl)-2,5,7,8-tetramethylchroman-6-yl 7-ethyl-camptothecin-10-yl succinate (IMP-III), hexadecyl 7-ethyl-camptothecin-10-yl succinate (IMP-IV), 2-(tetradecyloxycarbonyl)-2,5,7,8-tetramethylchroman-6-yl 7-ethyl-camptothecin-10-yl succinate (IMP-V), 4-(2-(hexadecyloxycarbonyl)-2,5,7,8-tetramethylchroman-6-yloxy)-4-oxobutanoic acid (IMP-VI), and 4-(2-(octodecyloxycarbonyl)-2,5,7,8-tetramethylchroman-6-yloxy)-4-oxobutanoic acid (IMP-VII). The probable origin of the impurities from the preparation process of TQ-B3203 was discussed. |
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| Keywords: | Antiproliferation camptothecin identification impurities synthesis TQ-B3203 |
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