Design and synthesis of a novel ZB716-d6 as a stable isotopically labeled internal standard

Abstract

ZB716 is a synthetic, steroidal, orally active anti-estrogen agent that is under clinical development for the treatment of estrogen receptor (ER)-positive metastatic breast cancer. The stable isotope-labeled ZB716 was required for use as an internal standard in LC-MS/MS assays. Therefore, a novel deuterated ZB716 (ZB716-d6) as an isotopically labeled internal standard was designed and synthesized through a newly developed route, which prepared ZB716-d6 in eight steps from the commercially available deuterium-labeled starting material [²H₆]pentafluoropentanol. This procedure is very practicable and gives the final compound in good yield (19% total yield) and high purity (D, >99%, chemical purity 98%). At present, ZB716-d6 has been successfully used as an internal standard in clinical bioanalysis.

Graphical Abstract

Keywords:

• Internal standard
• oral SERD
• stable isotope
• ZB716

Acknowledgement

We thank Drs. Changde Zhang and Qiang Zhang for recording the HRMS chromatograms and performing HPLC/MS purity analysis.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This research was funded by National Institute on Minority Health and Health Disparities (NIMHD), grant number 5U54MD007595-13.