Synthesis and characterization of radiolabeled 17β-estradiol conjugates

✍ Scribed by Suman L. Shrestha; Xuelian Bai; David J. Smith; Heldur Hakk; Francis X. M. Casey; Gerald L. Larsen; G. Padmanabhan

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: French
• Weight: 173 KB
• Volume: 54
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.1864

✦ Synopsis

The use of radioactive tracers for environmental fate and transport studies of emerging contaminants, especially for those that are labile, offers convenience in tracking study compounds and their metabolites, and in calculating mass balances. The aim of this study was to synthesize radiolabeled glucuronide and sulfate conjugates of 17b-estradiol (17b-E2). The conjugates 17b-[4-14 C]estradiol-3-glucuronide ([ 14 C]17b-E2-3-G) and 17b-[4-14 C]estradiol-17-sulfate ([ 14 C]17b-E2-17-S) were synthesized utilizing immobilized enzyme and chemical syntheses, respectively. Microsomal proteins from the liver of a phenobarbital induced pig (Sus scrofa domestica) were harvested and used to glucuronidate [ 14 C]17b-E2. Synthesis of [ 14 C]17b-E2-17-S consisted of a three-step chemical process -introducing a blocking group at the C-3 position of [ 14 C]17b-E2, sulfation at C-17 position, and subsequent deblocking to yield the desired synthetic product. Successful syntheses of [ 14 C]17b-E2-3-G and [ 14 C]17b-E2-17-S were achieved as verified by liquid chromatography, radiochemical analyses, quadrupole-time-of-flight (QTOF) mass spectrometry, and 1 H and 13 C nuclear magnetic resonance spectroscopy. Radiochemical yields of 84 and 44% were achieved for 17b-E2-3-G and 17b-E2-17-S, respectively. Synthetic products were purified using high-performance liquid chromatography and radiochemical purities of 98% or greater were obtained.