Liquid Chromatography-Mass Spectrometry to Monitor the Labeling Process Stability and Identify Derivatives during the Preparation of 188Re-MN-16ET: A Radiopharmaceutical for HepatomaWei-Hsi Chen1*, Pei-Cheng Wang1, Yu-Chieh Hsiao1, Tsai-Yueh Luo2, and I-Chung Tang2
- *Corresponding Author:
- Wei-Hsi Chen
Chemistry Division, Institute of Nuclear Energy Research
1000,Wunhua Rd, Jiaan Village, Longtan District
Taoyuan City, 32546, ROC, Taiwan
E-mail: [email protected]
Received date: February 03, 2017; Accepted date: February 18, 2017; Published date: February 24, 2017
Citation: Chen WH, Wang PC, Hsiao YC, Luo TY, Tang IC (2017) Liquid Chromatography-Mass Spectrometry to Monitor the Labeling Process Stability and Identify Derivatives during the Preparation of 188Re-MN-16ET: A Radiopharmaceutical for Hepatoma. Pharm Anal Chem 3:121. doi: 10.4172/2471-2698.1000121
Copyright: © 2017 Chen WH, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The labeling process stability of a radiopharmaceutical, radio isotope rhenium-labeled N-[2-mercaptoethyl]- 3-aza-19-ethyloxycarbonyl-3-[2-mercaptoethyl] octadecanoate (188Re-MN-16ET) for treatment of hepatocellular carcinoma (HCC) from its precursor, triphenylmethyl (Ph3C-) group protected-MN-16ET with 188ReO4- was surveyed and identified the derivatives from both reactant and product. After incubation for various specified periods of up to 6 h under various labeling reaction conditions, including acetic acid or mixed with normal saline, room temperature or a reaction temperature of 100°C, and the radiolytic effect of Re-188, the levels of protected-MN-16ET and Re-MN- 16ET in solutions were analyzed by high performance liquid chromatography-tandem mass spectrometry (HPLCMS/ MS) to study the impacts of the labeling process on their structural stabilities and the derivatives that arise from decomposition when preparing 188Re-MN-16ET from stock solution. This information is the key to determine whether 188Re-MN-16ET is structurally accurate and suitable for its intended use. The results showed that the major factor that impacts the structural stability of the product, Re-MN-16ET, is 188ReO4-; however, a thermal (100°C) effect on the precursor, protected-MN-16ET, was also observed. After 1 h incubation with 188ReO4- (100°C), the abundances of Re-MN-16ET and protected-MN-16ET were reduced by approximately 15% and 25%, respectively. The major decomposition products were Re-MN-16COOH and intra-molecular disulfide derivative. Moreover, the auto-radiolysis effect of Re-188 (60 mCi) on 188Re-MN-16ET was not clearly observable until 140 h. On the other hand, a stability study of Re-MN-16ET in plasma showed that 8% remained after incubation for 1 h; the metabolite was Re-MN-16COOH, which is identical to the hepatic bio-transformed product.