Identification and physicochemical characteristics of temozolomide process-related impurities

Molecules. 2013 Dec 11;18(12):15344-56. doi: 10.3390/molecules181215344.

Abstract

In this article the crystal structures of the starting material TZ-5 and the key intermediate TZ-6 of temozolomide (TZ-7), an anticancer therapeutic agent, are presented, together with their spectroscopic and thermal characteristics. Both compounds crystallize in the triclinic P-1 space group. X-ray crystallography studies proved that the compound TZ-6 exists as a monohydrate. A complete structural assignment was obtained for the signals in the 1H-, 13C- and 15N-nuclear magnetic resonance spectra and the structures were confirmed by Fourier-Transform infrared and Raman spectroscopy. The article describes the importance of the high purity of TZ-6 during the small-scale plant production of TZ-7 in a desired polymorphic form III with the purity higher than 99.50%, according to an HPLC method.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Alkylating / chemistry
  • Antineoplastic Agents, Alkylating / standards
  • Crystallography, X-Ray
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / chemistry
  • Dacarbazine / standards
  • Models, Molecular
  • Molecular Conformation
  • Nuclear Magnetic Resonance, Biomolecular
  • Spectrum Analysis, Raman
  • Temozolomide
  • Thermodynamics

Substances

  • Antineoplastic Agents, Alkylating
  • Dacarbazine
  • Temozolomide