Purity determinations in the bulk drug of the novel indoloquinone antitumor agent EO9

Abstract

The pharmaceutical development of the investigational cytotoxic drug EO9 included the structural characterization of the bulk drug by nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS) and infrared (IR) spectroscopy, and analytical characterization by high-performance liquid chromatography and ultraviolet/visible spectrophotometry. The presence of impurities in the bulk drug was investigated. The intermediates in the synthesis of EO9 were structurally characterized by NMR spectroscopy and MS, and analytically characterized by HPLC analysis with photodiode array (PDA) detection. All of the intermediates were below their limits of detection in EO9 bulk drug. The amounts of residual organic solvents were determined by gas chromatography. Methanol and ethanol were detected, but the amounts present did not exceed the limits as set in the United States Pharmacopeia XXII.

Simultaneous Quantitative Analysis of EO9 (Apaziquone) and its Conversion Products EO5a and EO9-Cl in Human and Dog Urine by High-Performance Liquid Chromatography Coupled with Electrospray Tandem Mass Spectrometry

“…Another degradation product, which was discovered by us and described earlier, is EO9 with covalently attached chlorine (EO9-Cl). It is formed in the acid-catalyzed reaction of EO9 in the presence of chloride anions in urine [6,7].…”